Search PubMed⌕ Search

Biomedical subjects

J H Simon

Publications and source records attributed to J H Simon.

At least 19 recordsLinked to original sources
PubMed2006

MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability.

BACKGROUND: Previous studies have shown only modest correlation between multiple sclerosis (MS) lesions on MRI and clinical disability. OBJECTIVE: To investigate the relationship between proton density/T2-weighted (T2) burden of disease (BOD) quantitatively measured on MRI scans and clinical determinants including disability. METHODS: Using the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) database, the authors studied baseline T2 BOD data from a pooled subsample of 1,312 placebo MS patients from 11 randomized controlled trials. Univariate comparisons guided development of multiple regression models incorporating the most important clinical predictors. RESULTS: Significant, although weak to moderate, correlations were found between T2 BOD and age at disease onset, disease duration, disease course, disability (as measured by the Expanded Disability Status Scale [EDSS]), relapse rate, certain presenting symptoms, and gadolinium enhancement. An unexpected but key finding that persisted in the multiple regression analyses was a plateauing relationship between T2 BOD and disability for EDSS values above 4.5. CONCLUSIONS: This study confirmed the limited correlation between clinical manifestations and T2 burden of disease (BOD) but revealed an important plateauing relationship between T2 BOD and disability.

Adult↗
PubMed2005

Predicting gadolinium enhancement status in MS patients eligible for randomized clinical trials.

BACKGROUND: Gadolinium enhancement is often used in randomized clinical trials to evaluate the efficacy of new drugs in multiple sclerosis (MS). Knowledge about predictors of enhancement status is important for the selection of patients for MRI monitored trials. METHODS: Data from 17 trials were available in anonymized format through the Sylvia Lawry Centre for MS Research. In an open part containing 1,328 (non primary progressive) patients, two logistic regression analyses were explored, including demographic, clinical, and MRI predictors. The authors examined the area under the curve (AUC) and the increase in positive predictive value (PPV). The final selection of models was validated in a closed part of 848 comparable patients. RESULTS: Age at onset, disease duration, and disease course (CIS/RR/SP) were important predictors from the multivariate models. Further, a multivariate model including T2 burden of disease was more predictive than one with only clinical predictors (AUC 0.719 vs 0.625, p < 0.001). For the model with T2 burden of disease, the PPV was 66.8%, compared to 58.5% for the model without (a priori chance 46.4%). These findings were unequivocally confirmed in the closed part of the database. CONCLUSION: Gadolinium status can be predicted by a set of baseline variables, certainly when T2 burden of disease is included. These findings may benefit the design and statistical power of future randomized clinical trials.

Adult↗
PubMed2003

Cytomegalovirus and Epstein-Barr virus DNA transcription in endodontic symptomatic lesions.

OBJECTIVES: Productive Herpesviridae infections are implicated in the etio-pathogenesis of aggressive periodontitis. However, virtually nothing is known about a possible role of herpesviruses in pulpal and periapical pathosis. This study employed a cDNA analysis to determine transcription of human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV) in 14 recalcitrant periapical lesions and in 2 periapical healthy control sites. METHODS: Periapical samples were collected in conjunction with periapical surgery and kept frozen until virologic examination. RNA was isolated from periapical tissue by using a guanidinium isothiocyanate-acid phenol procedure (TRIZOL LS Reagent, GIBCO BRL, Rockville, MD). cDNAs were amplified by means of oligonucleotides targeting highly conserved regions of the test viruses and the RT-PCR-100 amplification kit (Sigma-Aldrich, St Louis, MO). Standardization of PCR primer sensitivity and validation was carried out according to established methods. Amplification products were identified by agarose gel electrophoresis. RESULTS: HCMV transcript was detected in 12 of 13 symptomatic and in 1 asymptomatic periapical lesion. EBV transcript was demonstrated in 8 of the 13 symptomatic lesions but not in the asymptomatic periapical lesion. HCMV and EBV dual transcription occurred at higher frequency in periapical lesions showing radiographic bone destruction of 5 mm x 7 mm or larger than in smaller size lesions (P = 0.03; Chi-squared test). No HCMV or EBV transcription was identified in the 2 healthy control sites. HSV transcript was not detected in any study site. CONCLUSION: The present data suggest that HCMV or EBV infections participate in the pathogenesis of periapical symptomatic lesions. Herpesviruses may produce periapical pathosis as a direct result of viral infection and replication, or as a consequence of virally induced impairment of the host defense and subsequent increased virulence of resident bacterial pathogens.

Adult↗
PubMed2003

Cytomegalovirus and Epstein-Barr virus are associated with symptomatic periapical pathosis.

BACKGROUND: Recent studies have identified human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in symptomatic periapical lesions. Little information exists on HCMV and EBV in asymptomatic periapical lesions. AIM: To compare the presence of late transcripts of HCMV, EBV and herpes simplex virus (HSV) in symptomatic and asymptomatic periapical lesions. METHODS: Periapical samples were collected from seven symptomatic and seven asymptomatic periapical lesions at the time of apicoectomy. HCMV, EBV and HSV late mRNAs were identified by reverse transcription polymerase chain reaction. RESULTS: HCMV mRNA was detected in all seven symptomatic periapical lesions and in one asymptomatic lesion (Chi-squared test, Yates'P-value = 0.007). EBV mRNA was detected in six symptomatic lesions and in one asymptomatic lesion (P = 0.04). One asymptomatic lesion yielded HSV mRNA. CONCLUSIONS: HCMV and EBV active infections are associated with acute exacerbation of apical periodontitis. HSV seems to be unimportant in periapical pathosis.

Apicoectomy↗
PubMed2003

Cytomegalovirus and Epstein-Barr virus active infection in periapical lesions of teeth with intact crowns.

Herpesviruses seem to play an important role in the pathogenesis of aggressive periodontitis and may also contribute to periapical pathosis. This study determined the presence of human cytomegalovirus, Epstein-Barr virus, and herpes simplex virus productive infection in five symptomatic periapical lesions of teeth having intact crowns and calcified necrotic pulps. Periapical samples were collected in conjunction with periapical surgery and kept frozen until virological examination. Reverse transcription-polymerase chain reaction was used in herpesviral identification. RNA was isolated from periapical tissue by a guanidinium isothiocyanate-acid phenol procedure. cDNAs were generated from highly conserved regions of the test viruses using a preamplification kit. Sensitivity and validity of the PCR-primers were determined according to established methods. Amplification products were identified using gel electrophoresis. Human cytomegalovirus and Epstein-Barr virus dual transcription was detected in all five periapical lesions studied. Herpes simplex virus transcript was not identified in any lesion. The present data suggest that human cytomegalovirus or Epstein-Barr virus activation participate in the pathogenesis of symptomatic periapical lesions. We hypothesize that periapical active herpesvirus infection impairs local defenses, thereby inducing overgrowth of endodontopathic bacteria and the clinical flare-up of inflammation.

Cytomegalovirus↗
PubMed2002

Eight-year follow-up study of brain atrophy in patients with MS.

OBJECTIVE: To characterize whole-brain atrophy in relapsing-remitting MS (RRMS) patients over an 8-year period. The specific goals of this study were to determine if brain atrophy is related to subsequent disability status and to identify MRI correlates of atrophy progression. METHODS: A follow-up study was conducted to reassess patients from a phase III trial of interferon beta-1a (IFNbeta-1a) 8 years after randomization. Clinical and MRI data from 172 patients followed over 2 years in the original trial were used as baseline data. Follow-up data were obtained on 160 patients, including 134 patients with follow-up MRI examinations. Brain atrophy was estimated by automated calculation of brain parenchymal fraction. The relation between atrophy during the original trial and disability status at follow-up was determined. Correlations were also determined between lesion measurements from the original trial and the brain parenchymal fraction at follow-up. RESULTS: Brain atrophy was correlated with subsequent disability status. Atrophy rate during the original trial was the most significant MRI predictor of disability status at follow-up. Brain atrophy at follow-up was related to lesion volumes measured during the original trial. CONCLUSIONS: The relation between atrophy progression and subsequent neurologic disability status suggests that atrophy progression during RRMS is clinically relevant. Therefore, atrophy progression may be a useful marker for disease progression in clinical trials. The relation between lesions and subsequent atrophy indicates that brain atrophy may be related to focal tissue damage at earlier points in time, but important predisposing or other factors contributing to atrophy remain undefined.

Adjuvants, Immunologic↗
PubMed2002

Benefit of interferon beta-1a on MSFC progression in secondary progressive MS.

BACKGROUND: Interferon beta-1a (IFNbeta-1a, Avonex) is efficacious in relapsing forms of MS. Studies of other IFNbeta preparations in secondary progressive MS (SPMS) yielded conflicting results. This study was undertaken to determine whether IFNbeta-1a slowed disease progression in SP-MS. METHODS: A total of 436 subjects with SPMS and Expanded Disability Status Scale (EDSS) score 3.5 to 6.5 were randomized to receive IFNbeta-1a (60 micro g) or placebo by weekly intramuscular injection for 2 years. The primary outcome measure, used for the first time in a large-scale MS trial, was baseline to month 24 change in the MS Functional Composite (MSFC), comprising quantitative tests of ambulation (Timed 25-Foot Walk), arm function (Nine-Hole Peg Test [9HPT]), and cognition (Paced Auditory Serial Addition Test [PASAT]). RESULTS: Median MSFC Z-score change was reduced 40.4% in IFNbeta-1a subjects (-0.096 vs -0.161 in placebo subjects, p = 0.033), an effect driven mainly by the 9HPT and PASAT. There was no discernible benefit on the EDSS, which in this range principally reflects walking ability. IFNbeta-1a subjects had 33% fewer relapses (p = 0.008). There was significant benefit on eight of 11 MS Quality of Life Inventory subscales. New or enlarging T2-hyperintense brain MRI lesions and gadolinium-enhancing lesions were reduced at months 12 and 24 (both p < 0.001). IFNbeta-1a was well tolerated by the majority of subjects. Neutralizing antibodies developed in 3.3% of IFNbeta-1a-treated subjects. CONCLUSIONS: IFNbeta-1a demonstrated benefit on MSFC progression, relapses, quality of life, and MRI activity in SPMS.

Adjuvants, Immunologic↗
PubMed2001

Transcallosal bands: a sign of neuronal tract degeneration in early MS?

A pattern of injury observed in patients at high risk for MS described as transcallosal bands (TCB) is hypothesized to be the result of neuronal tract degeneration in earliest MS, extending from typical acute, focal demyelinating lesions located along the lateral borders of the corpus callosum. The TCB, a T2-hyperintense lesion traversing the corpus callosum is recognized on 3-mm thick, T2-weighted imaging, develops over months and persists over years.

Corpus Callosum↗
PubMed2001

Use of the multiple sclerosis functional composite as an outcome measure in a phase 3 clinical trial.

BACKGROUND: The Multiple Sclerosis Functional Composite (MSFC) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation (Timed 25-Foot Walk), arm function (9-Hole Peg Test), and cognitive function (Paced Auditory Serial Addition Test). The MSFC is the primary outcome measure in the ongoing multinational phase 3 trial of interferon beta-1a (Avonex) in patients with secondary progressive MS. OBJECTIVE: To assess the practice effects, reliability, and validity of the MSFC clinical outcome measure. DESIGN: Examining technicians underwent formal training using standardized materials. The MSFC was performed according to a standardized protocol. The 436 patients enrolled in the International Multiple Sclerosis Secondary Progressive Avonex Controlled Trial underwent 3 prebaseline MSFC testing sessions before randomization. RESULTS: Practice effects were evident initially for the MSFC but stabilized by the fourth administration. The Paced Auditory Serial Addition Test demonstrated the most prominent practice effects. The reliability of the MSFC was excellent, with an intraclass correlation coefficient for session 3 (final prebaseline session) vs session 4 (baseline) of 0.90. The MSFC at baseline correlated moderately strongly with the Kurtzke Expanded Disability Status Scale. Among the MSFC components, the Timed 25-Foot Walk correlated most closely. Correlations among the 3 MSFC components were weak, suggesting they assess distinct aspects of neurologic function in patients with MS. CONCLUSIONS: The MSFC demonstrated excellent intrarater reliability in this multinational phase 3 trial. Three prebaseline testing sessions were sufficient to compensate for practice effects. The pattern of correlations among the MSFC, its components, and the Kurtzke Expanded Disability Status Scale supported the validity of the MSFC.

Adult↗
PubMed2001

Esthesioneuroblastoma: the University of Iowa experience 1978-1998.

OBJECTIVE: Esthesioneuroblastoma is rare and the best treatment has yet to be defined. The purpose of this study is to analyze the natural history, treatment, and patterns of failure of esthesioneuroblastoma treated at one institution. METHODS: Between 1978 and 1998, 13 patients with esthesioneuroblastoma were identified using the University of Iowa Tumor Registry. All patients were staged according to Kadish criteria. Mean follow-up was 6.3 years. Six patients had 5 or more years of follow-up and four had follow-up exceeding 9.5 years. One patient was lost to follow-up at 36 months. RESULTS: No patients had Kadish stage A disease, five were stage B, and eight stage C. Overall actuarial 5- and 10-year survival rate was 61% and 24%, respectively. Disease-free survival rate at 5 and 10 years was 56% and 42%, respectively. Seven patients have died, three of intercurrent disease and three of disease progression, one with an unknown disease status. Six patients remain alive, three without evidence of disease and three have experienced a local or regional recurrence. Five patients who were initially controlled developed recurrence, three local only, one locoregional, and one regional and distant. Median time to failure was 96 months. All patients with follow-up exceeding 12 years have experienced either a local or regional recurrence. Survival after salvage therapy in these patients ranged from 3 to 12 years. CONCLUSION: Esthesioneuroblastoma has a long natural history characterized by frequent local or regional recurrence after conventional treatment. Successful retreatment can lead to prolonged survival.

Adult↗
PubMed2001

Brain and spinal cord atrophy in multiple sclerosis: role as a surrogate measure of disease progression.

Magnetic resonance imaging (MRI) reveals that brain and spinal cord atrophy occur early in the course of multiple sclerosis (MS), far earlier than originally anticipated. This has important implications for the early treatment of patients with MS, as atrophy is thought to reflect destructive, irreversible pathology, and subclinical impairment if not overt disability. Several recent trials in MS have included atrophy as a secondary or exploratory measure of treatment efficacy. While measured cerebral volume or spinal cord area changes are small over 1 to 3 year intervals, they are sufficiently large that with current methodologies the atrophy measures should provide conclusive information as to the effectiveness of therapeutic interventions in halting progressive atrophy. Atrophy measures may also provide an important metric for the evaluation of disease in primary progressive MS, and in testing combined therapies and neuroprotective agents, where conventional MRI methodologies may be relatively weak.

Atrophy↗
PubMed2000

Long-term effects in children treated with radiotherapy for head and neck rhabdomyosarcoma.

PURPOSE: To examine the long-term effects of treatment in children receiving radiotherapy for head and neck rhabdomyosarcoma. METHODS: From 1967 to 1994, a total of 30 children with head and neck rhabdomyosarcoma received megavoltage radiotherapy at one institution. Seventeen patients (57%) have survived and have at least a 5-year follow-up. There were 11 males and 6 females, with a median age of 5.7 years (range 2.2-11.6) at the time of radiotherapy. Tumor location was orbit in 6 patients, infratemporal fossa in 4, paranasal sinuses in 2, and supraglottic larynx in 2; the nasopharynx, pterygopalatine fossa, and parotid gland were sites for the remaining children. All but 2 patients had tumors of embryonal histology. The Intergroup Rhabdomyosarcoma Study (IRS) Group was I in 2, II in 3, and III in 11 children; 1 patient had a recurrent tumor after surgery alone. Radiotherapy volume was the primary tumor or tumor bed in 13, tumor and whole brain in 3, and tumor and craniospinal axis in 1. Median radiotherapy dose to the primary site was 5,040 cGy (range 4,140-6,500) and to the whole brain was 3,000 cGy. All but 1 were treated with 150-200-cGy fractions; 1 patient received 250-cGy fractions for a tumor in the larynx. Chemotherapy was vincristine (V), actinomycin-D (A), and cyclophosphamide (C) in 10 patients, VAC + adriamycin in 2, VA in 1, VA + ifosfamide in 1, VC + adriamycin in 1, and none in 2. One patient had salvage chemotherapy consisting of cisplatin and etoposide. Median follow-up time was 20 years (range 7.5-33). RESULTS: Late effects of treatment were seen in all patients and included facial growth retardation in 11, neuroendocrine dysfunction in 9, visual/orbital problems in 9, dental abnormalities in 7, hearing loss in 6, and hypothyroidism in 3. Intellectual and academic delays were documented in 3 patients who had received whole brain radiotherapy. While neuroendocrine, thyroid, dental, and cognitive sequelae were primarily attributed to radiotherapy, hearing loss was thought to be a direct result of tumor destruction and, in 1 case, cisplatin chemotherapy. Late effects at or beyond 10 years from radiotherapy were few, but severe, and included chondronecrosis, esophageal stenosis, second malignancy, and brain hemorrhage. CONCLUSION: Late effects of treatment in children receiving radiotherapy for head and neck rhabdomyosarcoma are frequent. Although radiotherapy is a significant contributor of neuroendocrine, dental, thyroid, and cognitive toxicity, it is not usually implicated with hearing loss. Late toxicity of treatment beyond 10 years is not as frequent as those occurring within 10 years of therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group.

BACKGROUND: Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value. METHODS: We conducted a randomized, double-blind trial of 383 patients who had a first acute clinical demyelinating event (optic neuritis, incomplete transverse myelitis, or brain-stem or cerebellar syndrome) and evidence of prior subclinical demyelination on magnetic resonance imaging (MRI) of the brain. After initial treatment with corticosteroids, 193 patients were randomly assigned to receive weekly intramuscular injections of 30 microg of interferon beta-1a and 190 were assigned to receive weekly injections of placebo. The study end points were the development of clinically definite multiple sclerosis and changes in findings on MRI of the brain. The trial was stopped after a preplanned interim efficacy analysis. RESULTS: During three years of follow-up, the cumulative probability of the development of clinically definite multiple sclerosis was significantly lower in the interferon beta-1a group than in the placebo group (rate ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.002). As compared with the patients in the placebo group, patients in the interferon beta-1a group had a relative reduction in the volume of brain lesions (P<0.001), fewer new or enlarging lesions (P<0.001), and fewer gadolinium-enhancing lesions (P<0.001) at 18 months. CONCLUSIONS: Initiating treatment with interferon beta-1a at the time of a first demyelinating event is beneficial for patients with brain lesions on MRI that indicate a high risk of clinically definite multiple sclerosis.

Adult↗
PubMed2000

A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon beta-1a. Multiple Sclerosis Collaborative Research Group.

BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFNbeta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. RESULTS: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r2 = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these lesions in the brain.

Adjuvants, Immunologic↗
PubMed2000

A Wallerian degeneration pattern in patients at risk for MS.

BACKGROUND: Demyelination alone may not explain the progressive disability that frequently develops in MS. An alternative explanation for irreversible disability assumes a contribution from axonal injury or loss. In theory, axonal injury may occur in the focal areas characterized by early inflammation, or can be more distant, as in Wallerian degeneration. However, Wallerian degeneration is thought of as a rare or a late finding in MS. METHODS: Studies showing a classic Wallerian degeneration pattern in the corticospinal tract were selected from a review of MR studies from patients enrolled in a longitudinal treatment trial. Entry was based on first occurrence of an isolated neurologic syndrome consistent with MS and a positive MRI. RESULTS: This report is based on five cases followed longitudinally who showed development of a classic T2-hyperintense lesion along the ipsilateral corticospinal tract, subsequent to an initial inciting event located in the white matter located in the superior aspect of the corona radiata. Lesions were evident as T2-hyperintensity persisting throughout the 12 to 18 months of observation. CONCLUSIONS: This series suggests that Wallerian degeneration, implying axonal injury, may occur as a sequela of acute demyelinating lesions in patients presenting with their first symptoms suggestive of MS. This can produce a component of the increasing burden of T2-hyperintense lesions temporally and spatially dissociated from inflammatory or demyelinating activity. Further studies are required to determine if Wallerian degeneration is an important factor contributing to disability progression in MS.

Adult↗
PubMed2000

Assessment of optic nerve damage in multiple sclerosis using magnetic resonance imaging.

The MR imaging-based assessment of the optic nerve in optic neuritis and multiple sclerosis provides information that is complementary to clinical and electrophysiological methods. The standard and more tissue destruction specific methods can be used in strategies to measure treatment efficacy and for understanding the mechanisms of relapse, recovery, and failure of recovery.

Humans↗