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Biomedical subjects

B Levine

Publications and source records attributed to B Levine.

At least 19 recordsLinked to original sources

Cavitary acetabular defects treated with morselized cancellous bone graft and cementless cups.

The use of impacted morselized cancellous bone grafts in conjunction with cementless hemispherical acetabular cups for treatment of AAOS type II acetabular cavitary deficiencies was evaluated in a retrospective study of 23 primary and 24 revision total hip arthroplasties, at a mean follow-up of 7.9 and 8.1 years, respectively. All primary hips received autografts, while all revision hips received allografts. Modified Harris Hip Scores for primary and revision hip replacements increased from a pre-operative mean of 37 and 47 to a postoperative mean of 90 and 86, respectively. All 23 autografts and 23 out of 24 cancellous allografts were radiographically incorporated without evidence of resorption. There were no instances of infection, component migration, or cases requiring subsequent acetabular revision. We conclude that impacted morselized cancellous bone-graft augmentation of cementless cups is a viable surgical option for AAOS type II cavitary acetabular defects.

Acetabulum↗

The functional neuroanatomy of classic delayed response tasks in humans and the limitations of cross-method convergence in prefrontal function.

Three classic delay tasks: spatial delayed response, delayed spatial alternation and delayed object-alternation are prototypical experimental paradigms for mapping the functional neuroanatomy of prefrontal cortex in animals. These tasks have been applied in human lesion studies, yet there have been very few studies investigating their functional neuroanatomy in healthy human subjects. We used functional magnetic resonance imaging to investigate the functional neuroanatomy of these classic paradigms (and a fourth: object delayed response) in a single sample of healthy human participants. Consistent with previous animal, human lesion, and functional neuroimaging studies, activity was observed in prefrontal and posterior parietal cortices across all three delay tasks. Task-specific activations, however, were not entirely consistent with predictions drawn from animal lesion studies. For example, delayed object-alternation activated dorsolateral prefrontal cortex, a region not generally implicated in animal lesion reports. Spatial delayed response, classically associated with the dorsolateral prefrontal cortex, did not activate this region; it rather activated posterior premotor cortices involved in response preparation, as did spatial alternation. All three tasks activated the frontopolar cortex, a region not considered crucial in animal research but associated with manipulation of internally generated information in recent human research. While cross-method convergence may be attained for lower level perceptual or motor tasks, the results of this study caution against the assumption that lesion-specific effects in animals generalize to human prefrontal cortex function.

Adult↗

Semiautomatic brain region extraction: a method of parcellating brain regions from structural magnetic resonance images.

Structural MR imaging has become essential to the evaluation of regional brain changes in both healthy aging and disease-related processes. Several methods have been developed to measure structure size and regional brain volumes, but many of these methods involve substantial manual tracing and/or landmark identification. We present a new technique, semiautomatic brain region extraction (SABRE), for the rapid and reliable parcellation of cortical and subcortical brain regions. We combine the SABRE parcellation with tissue compartment segmentation [NeuroImage 17 (2002) 1087] to produce measures of gray matter (GM), white matter (WM), ventricular CSF, and sulcal CSF for 26 brain regions. Because SABRE restricts user input to a few easily identified landmarks, inter-rater reliability is high for all volumes, with all coefficients between 0.91 and 0.99. To assess construct validity, we contrasted SABRE-derived volumetric data from healthy young and older adults. Results from the SABRE parcellation and tissue segmentation showed significant differences in multiple brain regions in keeping with regional atrophy described in the literature by researchers using lengthy manual tracing methods. Our findings show that SABRE is a reliable semiautomatic method for assessing regional tissue volumes that provides significant timesavings over purely manual methods, yet maintains information about individual cortical landmarks.

Adult↗

A robust method for extraction and automatic segmentation of brain images.

A new protocol is introduced for brain extraction and automatic tissue segmentation of MR images. For the brain extraction algorithm, proton density and T2-weighted images are used to generate a brain mask encompassing the full intracranial cavity. Segmentation of brain tissues into gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF) is accomplished on a T1-weighted image after applying the brain mask. The fully automatic segmentation algorithm is histogram-based and uses the Expectation Maximization algorithm to model a four-Gaussian mixture for both global and local histograms. The means of the local Gaussians for GM, WM, and CSF are used to set local thresholds for tissue classification. Reproducibility of the extraction procedure was excellent, with average variation in intracranial capacity (TIC) of 0.13 and 0.66% TIC in 12 healthy normal and 33 Alzheimer brains, respectively. Repeatability of the segmentation algorithm, tested on healthy normal images, indicated scan-rescan differences in global tissue volumes of less than 0.30% TIC. Reproducibility at the regional level was established by comparing segmentation results within the 12 major Talairach subdivisions. Accuracy of the algorithm was tested on a digital brain phantom, and errors were less than 1% of the phantom volume. Maximal Type I and Type II classification errors were low, ranging between 2.2 and 4.3% of phantom volume. The algorithm was also insensitive to variation in parameter initialization values. The protocol is robust, fast, and its success in segmenting normal as well as diseased brains makes it an attractive clinical application.

Adult↗

Functional reorganisation of memory after traumatic brain injury: a study with H(2)(15)0 positron emission tomography.

OBJECTIVE: To study the effects of moderate to severe traumatic brain injury (TBI) on the functional neuroanatomy supporting memory retrieval. METHODS: Subjects were six patients who had sustained a moderate to severe TBI about four years before scanning and had since made a good recovery. Eleven healthy young adults matched to the patients for age and education served as controls. An established H(2)(15)0 positron emission tomography paradigm was used to elicit brain activations in response to memory retrieval. TBI patients' patterns of brain activation were compared statistically with those of control subjects. Both group and individual case data were analysed. RESULTS: Both TBI patients and controls engaged frontal, temporal, and parietal regions known to be involved in memory retrieval, yet the TBI patients showed relative increases in frontal, anterior cingulate, and occipital activity. The hemispheric asymmetry characteristic of controls was attenuated in patients with TBI. Reduced activation was noted in the right dorsomedial thalamus. Although local aspects of this pattern were affected by the presence of focal lesions and performance differences, the overall pattern was reliable across patients and comparable to functional neuroimaging results reported for normal aging, Alzheimer's disease, and other patients with TBI. CONCLUSIONS: The TBI patients performed memory tasks using altered functional neuroanatomical networks. These changes are probably the result of diffuse axonal injury and may reflect either cortical disinhibition attributable to disconnection or compensation for inefficient mnemonic processes.

Adult↗

Interaction between carbon monoxide and ethanol in fire fatalities.

Impairment due to ethanol is clearly a risk factor in deaths due to fire. However, it is less clear whether there is a physiological interaction between ethanol and carbon monoxide (CO) that would alter the carboxyhemoglobin saturation level (COHb sat.) that accounts for death. In an attempt to explore this issue further, 196 fire fatalities investigated by the Office of the Chief Medical Examiner, State of Maryland over a 3-year period were examined. COHb sat. and blood ethanol concentrations (BAC) were tabulated. Twelve cases positive for therapeutic or abused drugs other than lidocaine or atropine were excluded; 184 cases were included. The data indicate that ethanol does not affect the COHb sat. that accounts for death, since the percentage of cases positive for ethanol at a given COHb range shows no trends. Therefore, we conclude that although ethanol remains a risk factor in fire fatalities, the risk appears to be related to the impairment that it produces as opposed to a direct interaction with CO.

Carboxyhemoglobin↗

Effect of storage temperature on endogenous GHB levels in urine.

Because gamma-hydroxybutyrate (GHB) is an endogenous substance present in the body and is rapidly eliminated after ingestion, toxicologists investigating drug-facilitated sexual assault cases are often asked to differentiate between endogenous and exogenous levels of GHB in urine samples. This study was designed to determine the effects of storage temperature on endogenous GHB levels in urine. Specifically, it was designed to ascertain whether endogenous levels can be elevated to a range considered indicative of GHB ingestion. Urine specimens from two subjects that had not been administered exogenous GHB were collected during a 24h period and individually pooled. The pooled specimens were separated into standard sample cups and divided into three storage groups: room temperature ( approximately 25 degrees C), refrigerated (5 degrees C), and frozen (-10 degrees C). Additionally, some specimens were put through numerous freeze/thaw cycles to mimic situations that may occur if multiple laboratories analyze the same specimen. Periodic analysis of the samples revealed increases in the levels of endogenous GHB over a 6-month period. The greatest increase (up to 404%) was observed in the samples maintained at room temperature. The refrigerated specimens showed increases of 140-208%, while the frozen specimens showed smaller changes (88-116%). The specimens subjected to multiple freeze/thaw cycles mirrored specimens that had been thawed only once. None of the stored urine specimens demonstrated increases in GHB concentrations that would be consistent with exogenous GHB ingestion.

Bias↗

Biologic consequences of Stat1-independent IFN signaling.

Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNgamma functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now demonstrate that both IFNgamma and IFNalpha/beta regulate proliferative responses in cells of the mononuclear phagocyte lineage derived from Stat1-null mice. Using both representational difference analysis and gene arrays, we show that IFNgamma exerts its Stat1-independent actions on mononuclear phagocytes by regulating the expression of many genes. This result was confirmed by monitoring changes in expression and function of the corresponding gene products. Regulation of the expression of these genes requires the IFNgamma receptor and Jak1. The physiologic relevance of IFN-dependent, Stat1-independent signaling was demonstrated by monitoring antiviral responses in Stat1-null mice. Thus, the IFN receptors engage alternative Stat1-independent signaling pathways that have important physiological consequences.

Animals↗

Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function.

Beclin 1 encodes a Bcl-2-interacting coiled-coil protein with autophagy and tumor suppressor function and is monoallelically deleted in 40-75% of sporadic human breast and ovarian cancers. Beclin 1 contains a leucine-rich nuclear export signal motif raising the possibility that its autophagy and/or tumor suppressor function may require regulated, CRM1-dependent, nucleocytoplasmic transport. In this study, we show that wild-type Beclin 1 colocalizes with both intracytoplasmic organelles and nuclei in COS7 monkey kidney and MCF7 human breast carcinoma cells. Inhibition of CRM1-dependent nuclear export with leptomycin B or mutation of the nuclear export signal motif of Beclin 1 results in predominantly nuclear localization. Unlike wild-type Beclin 1, the nuclear export mutant of Beclin 1 fails to promote nutrient deprivation-induced autophagy and fails to inhibit in vitro clonigenicity and in vivo tumorigenicity of MCF7 cells. Thus, beclin 1 has a leptomycin B-sensitive leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function. These findings suggest that the CRM1 nuclear export pathway may be important in the functional regulation of autophagic growth control.

Amino Acid Sequence↗

Stroop performance in focal lesion patients: dissociation of processes and frontal lobe lesion location.

There were three primary objectives: to examine the usefulness of the Stroop interference effect as a measure of frontal lobe function; to investigate the possibility of distinct lesion effects for word reading or color naming; and to specifically determine the brain regions necessary for the performance of the incongruent condition. Fifty-one patients with single focal brain lesions in frontal and non-frontal regions and 26 normal control subjects (CTL) were administered the word reading, color naming and incongruent conditions of the Stroop task. Only frontal lesions produced significant impairment. Patients with posterior lesions were not significantly deficient in any condition. Damage to the left dorsolateral frontal lobe resulted in increased errors and slowness in response speed for color naming. Contrary to Perret (Neuropsychology, 1974; 12: 323-330), lesions of the left frontal lobe did not result in a selective interference deficit on the Stroop incongruent condition. Rather, bilateral superior medial frontal damage was associated with increased errors and slowness in response time for the incongruent condition. This result is interpreted as failure of maintenance of consistent activation of the intended response in the incongruent Stroop condition. The results and conclusion are compatible with the prevalent theories of both the Stroop effect and the role of the superior medial frontal regions. The role of the anterior cingulate cortex on performance of the Stroop task is likely related to task and patient context.

Adult↗

Muscarinic versus nicotinic modulation of a visual task. a pet study using drug probes.

Little is known about acetylcholine (ACh) modulation of central visual processing in humans. Receptor densities in visual brain regions are differentially distributed suggesting that receptor subtypes have different functions. Using PET, we have previously described the brain regions activated by a simple pattern-flash stimulus in healthy elderly subjects. To evaluate muscarinic and nicotinic contributions to ACh modulation of visual processing, we scanned elderly subjects watching the pattern-flash stimulus during no drug, during physostigmine augmentation, and during scopolamine antagonism of physostigmine's action. These manipulations of ACh significantly altered regional cerebral blood flow (rCBF) in brain regions activated by the task. The pattern of rCBF values across drug conditions suggested that muscarinic and nicotinic effects were dissociated. Muscarinic action predominated in striate cortex (Brodmann Area, BA 17) and lateral visual association areas (BA 18, 19), while nicotinic action predominated in the thalamus and inferior parietal regions (BA 39/40). Both muscarinic and nicotinic actions increased rCBF in some regions while decreasing it in others. A parsimonious reconciliation of these results with functional anatomy suggests that muscarinic action modulates visual attribute processing, while nicotinic action modulates arousal and selective attention to the visual task.

Aged↗

Urine concentrations of ketamine and norketamine following illegal consumption.

Ketamine, an anesthetic agent primarily used in veterinary medicine and pediatrics, continues to gain in popularity in the drug abuse scene or 'Rave Wave' of all-night dance clubs. The Division of Forensic Toxicology Laboratory (Office of the Armed Forces Medical Examiner) at the Armed Forces Institute of Pathology, as the primary analytical laboratory for criminal investigative agencies in the Department of Defense (DOD), has seen requests for ketamine analysis rise from 1 in 1997 to 116 in 2000. This increasing abuse has led the DOD Urine Drug Testing Laboratories to consider adding ketamine screening to their random urinalysis program. However, before ketamine testing can be implemented as standard policy, concentrations of ketamine and metabolites in urine need to be evaluated after actual drug use. There is very little information regarding the pharmacokinetics of ketamine, especially concentrations of the drug or its two major metabolites, norketamine and dehydronorketamine, that can be expected in urine. In fact, dehydronorketamine has been believed to be an analytical artifact caused by the high temperatures of gas chromatography. In this paper, we attempt to resolve this issue with the development of a liquid chromatography-mass spectrometry (LC-MS) method. The urine concentrations of ketamine, norketamine and dehydronorketamine (presumptive) detected in 33 "positive" cases received in our laboratory since 1998 are reported. Quantitations were accomplished with LC-MS. Ketamine concentrations ranged from 6 to 7744 ng/mL. Norketamine concentrations ranged from 7 to 7986 ng/mL and dehydronorketamine (presumptive) concentrations ranged from 37 to 23,239 ng/mL.

Anesthetics, Dissociative↗

Citalopram distribution in postmortem cases.

This is a report of the analytical findings in 13 cases investigated by either the Office of the Chief Medical Examiner, State of Maryland or the Bexar County (San Antonio, TX) Medical Examiner's Office in which citalopram, a highly selective serotonin reuptake inhibitor used therapeutically as an antidepressant, was identified. In 8 of the 9 cases in which both blood and urine specimens were received, the urine citalopram concentration exceeded the blood concentration, indicating that urine is an appropriate specimen for screening citalopram use. The average liver to blood citalopram concentration ratio was 6.5 (range 3.1-13, n = 6). Three cases had blood concentrations less than 0.24 mg/L, which is in the reported antemortem therapeutic range of the drug. Eleven cases had blood concentrations less than 1.3 mg/L; in each of these cases, citalopram was determined to be an incidental finding to the ultimate cause of death. Quantitation of citalopram and the metabolite desmethylcitalopram in these cases yielded an average parent-to-metabolite ratio of 6.4.

Autopsy↗