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Biomedical subjects

J H Simon

Publications and source records attributed to J H Simon.

At least 37 records · Page 2Linked to original sources
PubMed2000

The contribution of spinal cord MRI to the diagnosis and differential diagnosis of multiple sclerosis.

Imaging considerations for the diagnosis and differential diagnosis of MS are based primarily on results of MR studies of the brain. Recent studies suggest that with current technology, MR imaging of the spinal cord can make important contributions, particularly in cases with equivocal or negative brain MRI studies. Spinal cord MRI may also assume an important role in early diagnosis.

Age Factors↗
PubMed2000

Quantitation of T2 lesion load in patients with multiple sclerosis: a novel semiautomated segmentation technique.

RATIONALE AND OBJECTIVES: The authors designed a segmentation technique that requires only minimal operator input at the initial and final supervision stages of segmentation and has computer-driven segmentation as the primary determinant of lesion boundaries. The technique was applied to compute total T2-hyperintense lesion volumes in patients with multiple sclerosis (MS). A semi-automated segmentation technique is presented and shown to have a test-retest reliability of <5%. MATERIALS AND METHODS: The method used a single segmented section with MS lesions. A probabilistic neural net performed segmentation into four tissue classes after supervised training. This reference section was deconstructed into the entire set of possible 4 x 4-pixel subregions, which was used to segment all-brain sections in steps of 4 x 4-pixel, adjacent image blocks. Intra- and interimage variabilities were tested by using 3-mm-thick, T2-weighted, dual-echo, spin-echo MR images from five patients, each of whom was imaged twice on the same day. Five different reference sections and three temporally separated. training sessions involving the same reference section were used to test the segmentation technique. RESULTS: The coefficient of variation ranged from 0.013 to 0.068 (mean +/- standard deviation, 0.037 +/- 0.039) for results from five different reference sections for each brain and from 0.007 to 0.037 (mean, 0.027 +/- 0.021) for brains segmented with the same reference section on three temporally separated occasions. Test-retest (intra-imaging) reliability did not exceed 5% (except for a small lesion load of 1 cm3 in one patient). Interimaging differences were approximately 10%. CONCLUSION: The segmentation technique yielded intra-imaging variabilities (2%-3%, except for very small MS lesion loads) that compare favorably with previously published results. New repositioning techniques that minimize imaging-repeat imaging variability could make this approach attractive for resolving MS lesion detection problems.

Algorithms↗
PubMed2000

The radicular groove: its potential clinical significance.

This report examines three clinical cases of root-filled teeth with primary endodontic lesions. During endodontic surgery, an area of incomplete root bifurcation beginning in the coronal or middle third of the root surface and terminating at or near the apical foramen were observed. The radicular grooves of two teeth were eliminated using a round bur ("saucerization"), and the resulting defect was filled with a bone substitute or calcium sulfate and covered by an absorbable collagen membrane. The other tooth was extracted, the groove was eliminated with a similar technique, and the tooth was replanted. Bacteria have been reported in chronic apical lesions. Our observations suggest that after conventional endodontic therapy, the etiology of a nonresolving primary endodontic lesion may be bacteria of endodontic origin sequestered within the protective confines of an apical-radicular groove.

Absorbable Implants↗
PubMed2000

Charcot-Leyden crystals within a periapical lesion.

Transmission electron microscopy revealed the presence of Charcot-Leyden crystals within a periapical lesion, which was assessed histopathologically as consistent with a periapical granuloma that failed to resolve after conventional endodontic treatment. This paper presents the clinical, radiographic, histological, and ultrastructural findings of this case and discusses their potential clinical significance.

Apicoectomy↗
PubMed2000

A twin MRI study of size variations in human brain.

Although it is well known that there is considerable variation among individuals in the size of the human brain, the etiology of less extreme individual differences in brain size is largely unknown. We present here data from the first large twin sample (N=132 individuals) in which the size of brain structures has been measured. As part of an ongoing project examining the brain correlates of reading disability (RD), whole brain morphometric analyses of structural magnetic response image (MRI) scans were performed on a sample of adolescent twins. Specifically, there were 25 monozygotic (MZ) and 23 dizygotic (DZ) pairs in which at least one member of each pair had RD and 9 MZ and 9 DZ pairs in which neither member had RD. We first factor-analyzed volume data for 13 individual brain structures, comprising all of the neocortex and most of the subcortex. This analysis yielded two factors ("cortical" and "subcortical") that accounted for 64% of the variance. We next tested whether genetic and environmental influences on brain size variations varied for these two factors or by hemisphere. We computed intraclass correlations within MZ and DZ pairs in each sample for the cortical and subcortical factor scores, for left and right neocortex, and for the total cerebral volume. All five MZ correlations were substantial (r's=.78 to.98) and significant in both samples, as well as being larger than the corresponding DZ correlations, (r's=0.32 to 0.65) in both samples. The MZ-DZ difference was significant for 3 variables in the RD sample and for one variable in the smaller control sample. These results indicate significant genetic influences on these variables. The magnitude of genetic influence did not vary markedly either for the 2 factors or the 2 hemispheres. There was also a positive correlation between brain size and full-scale IQ, consistent with the results of earlier studies. The total cerebral volume was moderately correlated (r=.42, p<.01, two-tailed) with full-scale IQ in the RD sample; there was a similar trend in the smaller control sample (r=.31, p<.07, two-tailed). Corrections of similar magnitude were found between the subcortical factor and full-scale IQ, whereas the results for the cortical factor (r=.16 and.13) were smaller and not significant. In sum, these results provide evidence for the heritability of individual differences in brain size which do not vary markedly by hemisphere or for neocortex relative to subcortex. Since there are also correlations between brain size and full-scale IQ in this sample, it is possible that genetic influences on brain size partly contribute to individual differences in IQ.

Adolescent↗
PubMed2000

Neuropsychological effects of interferon beta-1a in relapsing multiple sclerosis. Multiple Sclerosis Collaborative Research Group.

Cognitive dysfunction is common in multiple sclerosis (MS), yet few studies have examined effects of treatment on neuropsychological (NP) performance. To evaluate the effects of interferon beta-1a (IFNbeta-1a, 30 microg administered intramuscularly once weekly [Avonex]) on cognitive function, a Comprehensive NP Battery was administered at baseline and week 104 to relapsing MS patients in the phase III study, 166 of whom completed both assessments. A Brief NP Battery was also administered at 6-month intervals. The primary NP outcome measure was 2-year change on the Comprehensive NP Battery, grouped into domains of information processing and learning/memory (set A), visuospatial abilities and problem solving (set B), and verbal abilities and attention span (set C). NP effects were most pronounced in cognitive domains vulnerable to MS: IFNbeta-1a had a significant beneficial effect on the set A composite, with a favorable trend evident on set B. Secondary outcome analyses revealed significant between-group differences in slopes for Brief NP Battery performance and time to sustained deterioration in a Paced Auditory Serial Addition Test processing rate, favoring the IFNbeta-1a group. These results support and extend previous observations of significant beneficial effects of IFNbeta-1a for relapsing MS.

Adolescent↗
PubMed2000

Brain and spinal cord atrophy in multiple sclerosis.

Until recently, atrophy of the brain and spinal chord was thought to occur late in the course of multiple sclerosis (MS) or as a result of rare, fulminant disease. Now atrophy is known to occur early and likely indicates destructive and irreversible pathologic change that may be subclinical. Central nervous system atrophy from MS now can be measured accurately over short time intervals. Atrophy may become an important prognostic indicator in MS and is being evaluated as a treatment outcome measure in population studies, and possibly in the future, in individuals.

Atrophy↗
PubMed1999

Brain morphometry in reading-disabled twins.

OBJECTIVE: To test for brain structure differences in reading disability (RD) by means of MRI-based morphometry. BACKGROUND: Consensus is lacking on the brain structural correlates of RD. The current study reports on a wider set of structures in the largest sample yet studied, controlling for age, gender, IQ, and attention deficit hyperactivity disorder (ADHD). METHODS: A case-control study was performed that was comprised of 75 individuals with RD (mean age, 17.43+/-4.29 years) and 22 control subjects without RD (mean age, 18.69+/-3.75 years), each a single member of a twin pair. The two groups were similar in age, gender, and handedness, but differed in full-scale IQ (FSIQ), with the RD group having a lower mean FSIQ (101.8+/-9.9 versus 118.3+/-10.3). Using three group-by-structure analyses of covariance, groups were compared in terms of volume (in cubic centimeters) of major neocortical subdivisions, subcortical structures, and midsagittal areas (in square millimeters) of three subdivisions of the corpus callosum. RESULTS: Controlling for age, gender, and IQ, the authors found a significant group-by-structure interaction for the major neocortical subdivisions (p = 0.002), reflecting a different developmental pattern in the RD group, with the insula and anterior superior neocortex being smaller and the retrocallosal cortex being larger in the RD group. In contrast, they found no group main or interaction effects for the subcortical or callosal structures. The pattern of results was essentially the same in subjects without ADHD. CONCLUSIONS: Most brain structures do not differ in size in RD, but cortical development is altered subtly. This study replicates in a larger sample previous findings of insular differences in RD and demonstrates further that those differences are not attributable to comorbid ADHD.

Adolescent↗
PubMed1999

The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis.

MRI is very sensitive in showing MS lesions throughout the CNS. Using MRI for diagnostic purposes, however useful, is a complex issue because of limited specificity of findings and a variety of options as to when, how, and which patients to examine. Comparability of data and a common view regarding the impact of MRI are needed. Following a review of the typical appearance and pattern of MS lesions including differential diagnostic considerations, we suggest economic MRI examination protocols for the brain and spine. Recommendations for referral to MRI consider the need to avoid misdiagnosis and the probability of detecting findings of diagnostic relevance. We also suggest MRI classes of evidence for MS to determine the diagnostic weight of findings and their incorporation into the clinical evaluation. These proposals should help to optimize and standardize the use of MRI in the diagnosis of MS.

Brain↗
PubMed1999

A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).

OBJECTIVE: To determine if progressive brain atrophy could be detected over 1- and 2-year intervals in relapsing MS, based on annual MR studies from the Multiple Sclerosis Collaborative Research Group (MSCRG) trial of interferon beta-1a (Avonex). METHODS: All subjects had mild to moderate disability, with baseline expanded disability status scores ranging from 1.0 to 3.5, and at least two relapses in the 3 years before study entry. Atrophy measures included third and lateral ventricle width, brain width, and corpus callosum area. RESULTS: Significant increases were detected in third ventricle width at year 2 and lateral ventricle width at 1 and 2 years. Significant decreases in corpus callosum area and brain width were also observed at 1 and 2 years. Multiple regression analyses suggested that the number of gadolinium-enhancing lesions at baseline was the single significant contributor to change in third ventricle width. Atrophy over 1 and 2 years as indicated by enlargement of the third and lateral ventricle and shrinkage of the corpus callosum was greater for patients entering the trial with enhancing lesions. Greater disability increments over 1 and 2 years were associated with more severe third ventricle enlargement. CONCLUSION: In patients with relapsing MS and only mild to moderate disability, significant cerebral atrophy is already developing that can be measured over periods of only 1 to 2 years. The course of cerebral atrophy in MS appears to be influenced by prior inflammatory disease activity as indicated by the presence of enhancing lesions. Brain atrophy measures are important markers of MS disease progression because they likely reflect destructive and irreversible pathologic processes.

Adjuvants, Immunologic↗
PubMed1999

From enhancing lesions to brain atrophy in relapsing MS.

Based on observations from MR imaging studies, the natural history of the MS lesion appears to be progression from an acute enhancing lesion, corresponding to the early inflammatory stage, with evolution to a chronic T2 hyperintense lesion, which is the non-specific 'footprint' of the prior event. In addition to accumulation of these relatively non-specific lesions, we find in longitudinal evaluations that patients with only mild to modest disability are already developing significant cerebral atrophy. Atrophy, particularly that resulting from volume loss around the third ventricle, appears to be predicted by the presence of prior temporally and anatomically distant enhancing lesions. One can speculate that the initial enhancing-inflammatory lesion events in the brain, place into motion, at an early stage, the processes that ultimately lead to cerebral atrophy, and these processes may include early axonal injury.

Atrophy↗
PubMed1999

Cerebrospinal fluid abnormalities in a phase III trial of Avonex (IFNbeta-1a) for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group.

BACKGROUND AND OBJECTIVE: This report provides results of CSF analyses done in a subset of relapsing remitting MS patients participating in a placebo-controlled, double-blind, phase III clinical trial of IFNbeta-Studies supported by the National Multiple Sclerosis Society (grants RG2019, RG2827),a (Avonex , Biogen). The clinical trial demonstrated that IFNbeta-1a treatment resulted in significantly reduced disability progression, annual relapse rate, and new brain lesions visualized by cranial magnetic resonance imaging. The objectives of the current study were to determine: (a) whether CSF abnormalities in MS patients correlated with disease or MRI characteristics, and (b) effects of IFNbeta-1a therapy on these CSF abnormalities. METHODS: CSF was analyzed from 262 (87%) of the 301 study subjects at entry into the clinical trial, and a second CSF sample was analyzed from 137 of these 262 subjects after 2 years of therapy. CSF cell counts, oligoclonal bands (OCB), IgG index, and free kappa light chains were measured using standard assays. Baseline CSF results were compared with demographic, disease, and MRI parameters. Differences in on-study relapse rate, gadolinium enhancement, and EDSS change according to baseline CSF status was used to determine the predictive value of CSF for subsequent clinical and MRI disease activity. Change in CSF parameters after 104 weeks were used to determine the effects of treatment. RESULTS: (1) At study baseline, 37% of the subjects had abnormal CSF WBC counts, 61% had abnormal levels of CSF free kappa light chains, 84% had abnormal IgG index values, and 90% were positive for OCB. (2) Baseline IgG index, kappa light chains, and OCB showed weakly positive, statistically significant correlations with Gd-enhanced lesion volume and T2 lesion volume. WBC showed a statistically significant correlation with Gd-enhancing lesion volume but was uncorrelated with T2 lesion volume. (3) There was an associated between baseline CSF WBC counts and on-study clinical and MRI disease activity in placebo recipients. (4) IFNbeta-1a treatment resulted in significantly reduced CSF WBC counts, but there was no treatment-related change in CSF IgG index, kappa light chains, or OCB, which remained relatively stable over time in both patient groups. CONCLUSIONS: The current study documents significant reductions in CSF WBC counts in patients treated with IFNbeta-1a for 104 weeks. This finding is considered relevant to the therapeutic response, since CSF WBC counts were found to be positively correlated with subsequent clinical and MRI disease activity in placebo-treated relapsing MS patients.

Adjuvants, Immunologic↗
PubMed1999

Silent trauma.

Patients who present with discolored and/or symptomatic anterior teeth for which there are no obvious etiologic factors should be carefully questioned regarding their past surgical history. If the patient denies a history of trauma yet relates a recent, (2-5 years) history of undergoing general anesthesia, a differential diagnosis including trauma secondary to endotracheal intubation should be considered.

Anesthesia, Dental↗
PubMed1999

Vif and the p55(Gag) polyprotein of human immunodeficiency virus type 1 are present in colocalizing membrane-free cytoplasmic complexes.

The Vif protein of human immunodeficiency virus type 1 (HIV-1) is a potent regulator of viral infectivity. Current data posit that Vif functions late in replication to modulate assembly, budding, and/or maturation. Consistent with this model, earlier indirect immunofluorescence analyses of HIV-1-infected cells demonstrated that Vif and Gag colocalize to a substantial degree (J. H. M. Simon, R. A. M. Fouchier, T. E. Southerling, C. B. Guerra, C. K. Grant, and M. H. Malim, J. Virol. 71:5259-5267, 1997). Here, we describe a series of subcellular fractionation studies which indicate that Vif and the p55(Gag) polyprotein are present in membrane-free cytoplasmic complexes that copurify in sucrose density gradients and are stable in nonionic detergents. Both Vif and Gag are targeted to these complexes independent of each other, and their association with them appears to be mediated by protein-protein interactions. We propose that these complexes may represent viral assembly intermediates and that Vif is appropriately localized to influence the final stages of the viral life cycle and, therefore, the infectivity of progeny virions.

Cell Line↗
PubMed1999

Mutational analysis of the human immunodeficiency virus type 1 Vif protein.

Lentivirus Vif proteins are potent regulators of virus infectivity. However, relatively little is known about the functional domains, peptide motifs, or residues of any Vif protein. In this report, we present the first extensive mutagenesis analysis of the 192-amino-acid human immunodeficiency virus type 1 (HIV-1) Vif protein. A large number of scanning missense (mostly alanine substitution) and deletion mutations were introduced into the HIV-1HXB3 vif gene, and the resulting proteins were evaluated for the induction of virus infectivity as well as subcellular localization. The results show that amino acids dispersed throughout Vif's linear sequence are important for function. However, because many of the inactive proteins also appear to be mislocalized, we suggest that many of them may actually be misfolded rather lacking an intracellular targeting signal. Interestingly, disruptions within an internal region spanning residues 114 to 146 give rise to mutant proteins that either retain function or are inactive but are not substantially mislocalized. We therefore speculate that this region, which harbors two essential cysteine residues and one essential serine residue, may contain aspects of a putative Vif effector domain.

Amino Acid Sequence↗
PubMed1999

Elephant dental pulp tissue: where are the nerves?

Dental pulp tissue from three elephants was examined histologically with hematoxylin and eosin and s-100 protein stains. In all specimens, normal pulp was found with the exception that no nerve fibers (myelinated or non-myelinated) were demonstrable in any of the numerous sections prepared.

Animals↗
PubMed1999

Bimonthly cranial MRI activity following an isolated monosymptomatic demyelinating syndrome: potential outcome measures for future multiple sclerosis 'prevention' trials.

Patients with characteristic white matter lesions on MR imaging are at increased risk for the subsequent development of clinically definite MS (CDMS) following an isolated, monosymptomatic demyelinating syndrome (IMDS). These MR positive first-onset patients are thus candidates for MS prevention trials. Seven consecutive patients with IMDS and two or more periventricular and/or oval lesions on MR imaging were enrolled into a prospective trial based on serial T2-weighted and enhanced MR imaging at two month intervals for 12 - 15 months. Forty-seven new enhancing lesions were detected with triple dose MR contrast compared to 31 lesions using the standard dose. Four of the seven patients accounted for 98% of all enhancing lesions in this study, while the remaining three patients showed little MRI or clinical disease activity. New T2 lesion counts correlated strongly with enhanced lesion counts (r=0.82 - 0.98). We detected 49 new T2-hyperintense (T2) lesions based on short-interval (2 monthly) follow-up, and 31 new T2-lesions comparing exit and entry examinations. These results suggest several potential MR-based strategies for evaluating first onset patients in a phase III MS prevention trial. Since these patients have a small average T2-lesion load, it is quite easy to visually detect new T2 lesions. As a result, at a bimonthly study interval, T2-weighted lesion analysis is an effective measure of cumulative disease activity, provided high-resolution T2-weighted imaging studies are acquired to quantitate new T2-lesions. Enhanced lesion activity remains an important measure of blood - brain - barrier breakdown and may predict short term MRI and clinical disease activity in IMDS patients.

Adult↗