J D Glass

Publications (45)355.34 Total impact

• Article: Localization of HIV-1 DNA and tumor necrosis factor-alpha mRNA in human brain using polymerase chain reaction in situ hybridization and immunocytochemistry.

  S L Wesselingh, J D Glass
  Methods in molecular biology (Clifton, N.J.) 02/2000; 123:323-37.
• Article: Viral load in HIV-associated dementia.

  J D Glass, S L Wesselingh
  Annals of Neurology 08/1998; 44(1):150-1. · 11.09 Impact Factor
• Source

  Available from: Shikha Mittoo

  Article: Brain-derived HIV-1 tat sequences from AIDS patients with dementia show increased molecular heterogeneity.

  A C Bratanich, C Liu, J C McArthur, T Fudyk, J D Glass, S Mittoo, G A Klassen, C Power
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  ABSTRACT: HIV-1 infection results in a dementing illness affecting 20% of patients with AIDS. Several HIV-1 genes have been implicated in the pathogenesis of HIV-induced neurological disease. To search for distinct HIV-1 sequences associated with the development of dementia, brain-derived tat, env, and pol sequences were examined from AIDS patients defined pre-mortem as demented (HIV-D)[n=5] or non-demented (HIV-ND)[n=5]. Estimations of evolutionary distances and frequency of non-synonymous mutation rates revealed significant differences between brain-derived tat, env, and pol-encoded reverse transcriptase sequences. However, established zidovudine-associated resistance mutations in reverse transcriptase sequences were identified in only one HIV-D and one HIV-ND patient despite prolonged treatment of some patients. Non-synonymous/synonymous substitution rates among the tat sequences derived from patients with HIV-D were significantly higher compared to the HIV-ND group (P < 0.001). The ratios of transversions to transitions were also significantly higher among the HIV-D tat sequences (P< 0.01). Phylogenetic analyses showed clustering of sequences from each clinical group among the brain-derived tat and env sequences. These studies indicated that differing selective forces act on individual HIV-1 genes in the brain which may influence the development of dementia.
  Journal of NeuroVirology 08/1998; 4(4):387-93. · 2.31 Impact Factor
• Article: Cloning of m-calpain 80 kD subunit from the axonal degeneration-resistant WLD(S) mouse mutant.

  J D Glass, N Nash, I Dry, D Culver, A I Levey, S Wesselingh
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  ABSTRACT: Calpains are calcium-activated cysteine proteases that are involved in cellular degradation in models of neurodegeneration. Calpains are the effectors of cytoskeletal disruption during axonal degeneration, a pathological feature of many neurological disorders. The WLD(S) mouse mutant is resistant to axonal degeneration and demonstrates prolonged survival of the cytoskeleton after nerve injury. To investigate the possibility that a mutation in calpain or abnormalities in calpain protein expression is responsible for the resistance to axonal degeneration seen in the WLD(S) mouse mutant, we 1) cloned and sequenced the large subunit of the high calcium-requiring form of calpain (m-calpain) from nervous system tissues of WLD(S) and from wild-type C57BL/6 mice, and 2) generated polyclonal m-calpain antibodies for comparison of relative protein levels by Western blot. We found our sequence for mouse m-calpain to be almost identical to another recently published mouse sequence, and the wild-type and WLD(S) sequences to be identical. Our fusion protein and peptide polyclonal antibodies were specific for the 80 kD subunit and recognized appropriate protein bands from pure m-calpain, fusion protein, and in tissue. There was no apparent difference in m-calpain expression in nerve or spinal cord in noninjured adult animals. These data suggest that a defect in m-calpain 80 kD subunit does not likely underlie the WLD(S) phenotype, but raise questions about other subunits of calpain and possibly other proteases.
  Journal of Neuroscience Research 07/1998; 52(6):653-60. · 2.74 Impact Factor
• Article: Variable progression of HIV-associated dementia.

  F H Bouwman, R L Skolasky, D Hes, O A Selnes, J D Glass, T E Nance-Sproson, W Royal, G J Dal Pan, J C McArthur
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  ABSTRACT: A consecutive series of 71 patients diagnosed with HIV-associated dementia (HAD) (1984-1994) were studied to characterize the clinical course of HAD, and to identify predictive markers of rapid neurologic progression. Neurologic progression rate was determined from the change in the Memorial Sloan Kettering (MSK) dementia severity score from diagnosis to death. Those with the most rapid progression in neurologic disability were compared with those with slow or no progression. Autopsy material was immunostained for macrophage activation markers and gp41 in 30 individuals. Median survival was 3.3 months and 6.1 months for rapid-progression and no-progression patients, respectively. Rapid progression was associated with injection drug use but not with race, gender, or age. CD4+ cell counts were lower at diagnosis among rapid-progression than no-progression patients but no differences in AIDS-defining illnesses or patterns of antiretroviral therapy were found. At presentation, rapid-progression patients had more prominent symptoms of mental slowing than those with no progression; however, no other clinical features, CSF, or imaging features distinguished the groups. Less abundant macrophage activation in both basal ganglia and midfrontal gyrus regions, as judged by HAM56 immunostaining, was noted in 9 no-progression patients, compared with 12 rapid-progression patients. Neurologic progression and survival with HAD is highly variable. A significant proportion of individuals with dementia have prolonged survival of more than 12 months and remain cognitively stable. A history of injection drug use and presentation with prominent psychomotor slowing is associated with more rapid neurologic progression, and these patients tend to show more abundant macrophage activation within the CNS.
  Neurology 07/1998; 50(6):1814-20. · 8.31 Impact Factor
• Article: Cellular localization of tumor necrosis factor mRNA in neurological tissue from HIV-infected patients by combined reverse transcriptase/polymerase chain reaction in situ hybridization and immunohistochemistry.

  S L Wesselingh, K Takahashi, J D Glass, J C McArthur, J W Griffin, D E Griffin
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  ABSTRACT: HIV-induced neurological disease is postulated to be caused by indirect mechanisms. Tumor necrosis factor (TNF)alpha is increased in the brains in human immunodeficiency virus (HIV)-associated dementia and in the spinal cord in vacuolar myelopathy and may play a pathogenetic role in these diseases. Microglia, astrocytes and infiltrating macrophages can be induced to produce TNF alpha and each has been identified as a source of TNF alpha in neurological disease. Reverse transcriptase synthesis of cDNA and polymerase chain reaction amplification of the cDNA was combined with immunocytochemistry to identify the cellular source of TNF alpha in HIV-induced neurological disease. Cells positive for TNF alpha mRNA were more abundant in white matter than gray matter of the brain from demented individuals. TNF alpha mRNA-positive cells in brains and spinal cords were almost exclusively macrophage-lineage cells. Only rare TNF alpha mRNA-positive cells were astrocytes. We conclude that macrophage-lineage cells are the primary source of elevated central nervous system TNF alpha mRNA in providing further evidence that macrophage activation is an important element in the pathogenesis of HIV-associated neurological disease.
  Journal of Neuroimmunology 05/1997; 74(1-2):1-8. · 2.96 Impact Factor
• Article: Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41.

  D C Adamson, B Wildemann, M Sasaki, J D Glass, J C McArthur, V I Christov, T M Dawson, V L Dawson
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  ABSTRACT: Indirect mechanisms are implicated in the pathogenesis of the dementia associated with human immunodeficiency virus-type 1 (HIV-1) infection. Proinflammatory molecules such as tumor necrosis factor alpha and eicosanoids are elevated in the central nervous system of patients with HIV-1-related dementia. Nitric oxide (NO) is a potential mediator of neuronal injury, because cytokines may activate the immunologic (type II) isoform of NO synthase (iNOS). The levels of iNOS in severe HIV-1-associated dementia coincided with increased expression of the HIV-1 coat protein gp41. Furthermore, gp41 induced iNOS in primary cultures of mixed rat neuronal and glial cells and killed neurons through a NO-dependent mechanism. Thus, gp41-induced NO formation may contribute to the severe cognitive dysfunction associated with HIV-1 infection.
  Science 01/1997; 274(5294):1917-21. · 31.20 Impact Factor
• Article: Stereological analysis of cerebral atrophy in human immunodeficiency virus-associated dementia.

  P Subbiah, P Mouton, H Fedor, J C McArthur, J D Glass
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  ABSTRACT: Brain atrophy is a common finding in patients with AIDS, but the relationship of atrophy to HIV-associated dementia is unclear. We used unbiased, stereological methods on postmortem brain specimens to estimate volumes of different brain regions in patients prospectively diagnosed with and without HIV-associated dementia. Thirty HIV-seropositive (9 without AIDS/without dementia, 6 with AIDS/without dementia, 15 with AIDS/with dementia) and 7 HIV-seronegative controls were studied using the technique of point counting and Cavalieri's principle of volume estimation. There was a significant reduction in the mean neocortical volume (15%, p = 0.032) in the group with AIDS when compared to the seronegative controls, and this difference was accentuated when comparing only the group with HIV-associated dementia to the seronegatives (neocortex: 18%, p = 0.020). There were no significant differences between the AIDS groups with and without HIV-associated dementia, although there was a trend for smaller volumes in the most severely demented patients. There were no differences in white matter volumes between groups. In conclusion, patients dying with AIDS and particularly those with HIV-associated dementia, show significant neocortical atrophy when compared to seronegative controls. The lack of a significant difference in cerebral atrophy between HIV-seropositive patients with and without dementia suggests that atrophy may be a more generalized phenomenon of AIDS as opposed to a specific marker for HIV-associated dementia.
  Journal of Neuropathology and Experimental Neurology 11/1996; 55(10):1032-7. · 4.26 Impact Factor
• Article: Localization of HIV-1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry.

  K Takahashi, S L Wesselingh, D E Griffin, J C McArthur, R T Johnson, J D Glass
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  ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) infects the brains of a majority of patients with the acquired immunodeficiency syndrome (AIDS), and has been linked to the development of a progressive dementia termed "HIV-associated dementia." This disorder results in severe cognitive, behavioral, and motor deficits. Despite this neurological dysfunction, HIV-1 infection of brain cells does not occur significantly in neurons, astrocytes, or oligodendrocytes, but is restricted to brain macrophages and microglia. To identify possible low-level or latent infection of other brain cells, we combined the techniques of the polymerase chain reaction with in situ hybridization for the detection of HIV DNA, and used immunocytochemistry to identify the HIV-expressing cells. In the 21 adult brains studied (15 AIDS and 6 seronegative control brains), we found that polymerase chain reaction/in situ hybridization was both sensitive and specific for identifying HIV-infected cells. In all brains, the majority of infected cells were macrophages and microglia. In several brains, however, a substantial minority of cells harboring HIV DNA were identified as astrocytes. Neurons, oligodendrocytes, and endothelial cells were not infected with HIV, even in cases with HIV-associated dementia. These findings confirm previous data regarding the importance of macrophage/microglial infection, and essentially exclude neuronal infection in pathogenetic models of HIV-associated neurological disease. These data also demonstrate that latent or low-level infection of astrocytes occurs in AIDS, a finding that may be of importance in understanding HIV neuropathogenesis.
  Annals of Neurology 07/1996; 39(6):705-11. · 11.09 Impact Factor
• Article: Quantitation of human immunodeficiency virus in brains of demented and nondemented patients with acquired immunodeficiency syndrome.

  R T Johnson, J D Glass, J C McArthur, B W Chesebro
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  ABSTRACT: We measured human immunodeficiency virus (HIV) DNA in brains of 15 patients who died with acquired immunodeficiency syndrome (AIDS). All had been followed prospectively prior to death; 7 were demented and 8 were not demented. HIV was detected in 13 of 15 brains by polymerase chain reaction (PCR) and in the remaining 2 by presence of viral RNA or viral antigen. Quantitative PCR showed a wide range in amounts of HIV DNA with no significant difference between brains of demented and nondemented patients. These results suggest that qualitative features of the virus, rather than increased virus load per se, may be responsible for the clinical differences between HIV-infected patients with and without dementia.
  Annals of Neurology 04/1996; 39(3):392-5. · 11.09 Impact Factor
• Article: Human immunodeficiency virus and the brain.

  J D Glass, R T Johnson
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  ABSTRACT: Human immunodeficiency virus (HIV) infects the nervous system in the majority of patients, causing a variety of neurological syndromes throughout the course of the disease. This review focuses on the effects of HIV in the central nervous system, with an emphasis on HIV-associated dementia. HIV-associated dementia occurs in a subset of patients with AIDS; it is unclear why these patients and not all patients develop the disease. Several factors are likely to be involved in the pathogenesis of HIV-associated dementia, including neurotoxins released from the virus and/or infected macrophages and microglia, immunologic dysregulation of macrophage function, and specific genetic strains of HIV. These factors, and their possible interactions, are discussed.
  Annual Review of Neuroscience 02/1996; 19:1-26. · 25.74 Impact Factor
• Article: A potential role for interferon-alpha in the pathogenesis of HIV-associated dementia.

  M B Rho, S Wesselingh, J D Glass, J C McArthur, S Choi, J Griffin, W R Tyor
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  ABSTRACT: Previous studies in patients receiving interferon-alpha (IFN-alpha) therapy and patients with systemic lupus erythematosus have demonstrated that elevated cerebrospinal fluid (CSF) levels of IFN-alpha are associated with cognitive dysfunction. We measured IFN-alpha levels in CSF and blood by ELISA in human immunodeficiency virus (HIV)-positive patients with (n = 21) and without (n = 23) dementia and HIV-negative controls (n = 48). IFN-alpha was significantly elevated in the CSF of HIV-positive patients with dementia compared to those without dementia and controls. An increasing amount of IFN-alpha in the CSF was correlated with the clinical parameter of increasing Memorial Sloan Kettering scores; although these correlations were not statistically significant, they further suggest an association of increased CSF IFN-alpha with neurocognitive dysfunction in AIDS. Immunocytochemical staining of brains demonstrated IFN-alpha-positive macrophages and astrocytes in frontal cortex and white matter and IFN-alpha mRNA was detected by reverse transcriptase-polymerase chain reaction, further indicating that IFN-alpha is made by cells within the brain and suggesting that the significant increases of IFN-alpha protein found in the CSF of patients with HIV-associated dementia complex are derived from intrinsic brain cells such as macrophages and astrocytes. Increased local production of IFN-alpha during HIV infection may contribute directly or indirectly to the pathogenesis of HIV-associated dementia.
  Brain Behavior and Immunity 01/1996; 9(4):366-77. · 4.72 Impact Factor
• Article: Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia.

  J D Glass, H Fedor, S L Wesselingh, J C McArthur
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  ABSTRACT: The pathogenesis of human immunodeficiency virus (HIV)-associated dementia is unclear, and the underlying pathological substrate has been a matter of debate. In a prospectively clinically characterized population of acquired immunodeficiency syndrome (AIDS) patients we investigated the relationship between the clinical syndrome of HIV-associated dementia and the presence and relative quantity of immunocytochemical markers for HIV-1 (gp41 antibody), and for macrophages and microglia (HAM-56 antibody). Sections from the basal ganglia and frontal lobes from the brains of 51 patients were studied, and the data were stratified for severity of dementia (16 nondemented, 12 mildly demented, 23 severely demented), rate of dementia progression, duration of AIDS, use of antiretrovirals, and several other demographic features. We found a highly significant correlation between the degree of macrophage staining and the severity of dementia but only a borderline correlation between the presence and amount of gp41-positive cells and dementia. Several nondemented patients showed abundant gp41 immunoreactivity, and some severely demented showed little to no gp41 immunoreactivity. Other correlations with the immunostaining data, including antiretroviral use, were not significant. We conclude that the presence of macrophages and microglia is a better correlate with HIV-associated dementia than is the presence and amount of HIV-infected cells in the brain. These data support the concept that the pathogenesis of HIV-associated dementia is likely due to indirect effects of HIV infection of the brain, possibly through the actions of macrophages and microglia.
  Annals of Neurology 12/1995; 38(5):755-62. · 11.09 Impact Factor
• Source

  Available from: jneurosci.org

  Article: Axotomy-induced axonal degeneration is mediated by calcium influx through ion-specific channels.

  E B George, J D Glass, J W Griffin
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  ABSTRACT: We examined the role of extracellular calcium entry, the possible involvement of axonal calcium channels, and the potential protective effect of calcium channel and calpain antagonists in axotomy-induced axonal degeneration using murine dorsal root ganglia in cell culture. We found that calcium entry is both necessary and sufficient to induce axonal degeneration after axotomy, and may be inhibited by cobalt, manganese, dihydropyridines, and bepridil. Tetrodotoxin and omega-conotoxin are ineffective in preventing axonal degeneration. The activation of calpains also appears to be necessary and sufficient for axonal degeneration to proceed, and can be blocked with membrane-permeant leupeptin analogs and the oxirane aloxistatin. Although other calcium-activated events may occur, it appears that inhibition of calpain is sufficient to preserve the axon at the light microscope level, and to prevent axonal cytoskeleton degradation as detected by immunofluorescent staining. Our results suggest that axonal degeneration after axotomy involves the following sequence of events: (1) a lag-period after axotomy prior to the onset of axonal degeneration, (2) entry of calcium into the axon through an intact axolemma via a calcium-specific ion transport mechanism, (3) activation of calcium-dependent effector molecules such as calpains, (4) degradation of the axonal cytoskeleton. The details of the second step require further elucidation, and are of particular interest because this step is a potential target for therapies directed towards peripheral neuropathies.
  Journal of Neuroscience 11/1995; 15(10):6445-52. · 7.11 Impact Factor
• Article: Prolonged axonal survival in transected nerves of C57BL/Ola mice is independent of age.

  T O Crawford, S T Hsieh, B L Schryer, J D Glass
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  ABSTRACT: Interrupted nerve fibres from the C57BL/Ola strain of mouse degenerate after an extraordinary delay compared to nerves of standard laboratory mice. Other investigators, using electrophysiologic methods, concluded that the mutant phenotype diminishes with age, implying that the mutation in C57BL/Ola mice affects a developmentally regulated gene. In an effort to confirm this observation, we studied the course of Wallerian degeneration in C57BL/Ola mice aged 1 through 16 months by using quantitative morphometry, immunohistochemistry, and immunoblotting, but found the period of axonal survival after nerve transection to be no different in old versus young C57BL/Ola mice. We conclude that the C57BL/Ola phenotype of prolonged survival of transected nerves is not affected by age, although certain physiologic measures may degrade in older animals. The persistence of axoplasm after nerve injury in C57BL/Ola mice may be the feature most closely related to the function of the mutant gene.
  Journal of Neurocytology 06/1995; 24(5):333-40. · 1.94 Impact Factor
• Article: Autosomal dominant distal spinal muscular atrophy in four generations.

  K B Boylan, D R Cornblath, J D Glass, K Alderson, R W Kuncl, P W Kleyn, T C Gilliam
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  ABSTRACT: Distal spinal muscular atrophy is a rare lower motor neuron disorder that may be difficult to distinguish clinically from type II Charcot-Marie-Tooth disease. We report on clinical and pathologic findings in 13 members of a four-generation extended family with autosomal dominant distal spinal muscular atrophy. The patients developed a slowly progressive lower motor neuron disorder involving mainly the distal lower extremities; onset was from the second to fourth decades. Electromyography and muscle biopsy findings were indicative of motor denervation. Combined silver/cholinesterase/immunocytochemical staining of intramuscular nerve revealed abundant collateral axonal branching in mild disease but marked loss of terminal motor endplate innervation in the more severe state, suggesting decreased growth of motor axon collaterals with disease progression. Multipoint DNA linkage analysis showed that this family's disorder is not linked to the chromosome 5q11.2-13.3 spinal muscular atrophy locus.
  Neurology 05/1995; 45(4):699-704. · 8.31 Impact Factor
• Article: Distinct HIV-1 env sequences are associated with neurotropism and neurovirulence.

  C Power, J C McArthur, R T Johnson, D E Griffin, J D Glass, R Dewey, B Chesebro
  Current topics in microbiology and immunology 02/1995; 202:89-104. · 4.93 Impact Factor
• Article: Clinicopathologic correlations of HIV-1-associated vacuolar myelopathy: an autopsy-based case-control study.

  G J Dal Pan, J D Glass, J C McArthur
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  ABSTRACT: To determine the clinical correlates of HIV-1-associated vacuolar myelopathy (VM), we designed a case-control study based on 215 AIDS autopsies in which we examined the spinal cord. We defined a case as an individual dying with AIDS and with VM present at autopsy; we defined a control as an individual dying with AIDS without VM. VM was found in 100 of 215 (46.5%) autopsies, with no apparent temporal trends. A higher number of AIDS-defining illnesses was strongly associated with the likelihood of VM (trend chi-square = 26.52, p < 0.001). Systemic infection with Mycobacterium avium-intracellulare and Pneumocystis carinii pneumonia were each associated with the pathologic findings of VM in both univariate and multivariate models. In the brain, multinucleated giant cells were detected in more cases than in controls (odds ratio = 3.68, 95% CI = 1.73 to 7.47, p < 0.001). The clinical features of HIV-1 dementia were not associated with VM; in contrast, predominantly sensory neuropathy was more common in VM cases than in controls (odds ratio = 5.00, 95% CI = 1.35 to 18.5, p < 0.05). Fifty-six cases with VM had detailed neurologic evaluations, but only 15 (26.8%) had signs and symptoms of myelopathy. The presence of symptomatic myelopathy was related to the pathologic severity: none of 17 cases with grade 1, five of 26 with grade 2, and 10 of 13 with grade 3 had clinical features of myelopathy (trend chi-square = 21.16, p < 0.005). VM is a common neuropathologic finding that is frequently unrecognized during life. The association with the number of systemic illnesses, M avium-intracellulare infection, and P carinii pneumonia suggests that the development of VM is related to the severity of immunosuppression.
  Neurology 11/1994; 44(11):2159-64. · 8.31 Impact Factor
• Article: Chronic inflammatory demyelinating polyneuropathy and paraproteinemic neuropathies.

  J D Glass, D R Cornblath
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  ABSTRACT: Chronic inflammatory demyelinating polyneuropathy and the neuropathies associated with monoclonal gammopathies represent a significant proportion of initially undiagnosed neuropathies. Over the past year, a number of publications have provided information on the clinical characteristics, mechanisms, and possible relationships between these neuropathies. This review summarizes this recent information, with an emphasis on the relevance to therapy.
  Current Opinion in Neurology 11/1994; 7(5):393-7. · 4.94 Impact Factor
• Article: Inter- and intraexaminer reliability of nerve conduction measurements in patients with diabetic neuropathy.

  V Chaudhry, A M Corse, M L Freimer, J D Glass, E D Mellits, R W Kuncl, S A Quaskey, D R Cornblath
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  ABSTRACT: We determined the inter- and intraexaminer reliability of nerve conduction measurements in six patients with diabetic peripheral neuropathy. Each patient was examined by six electromyographers on two separate occasions at least 1 week apart. We obtained attributes of nerve conduction at each examination and analyzed the data by analysis of variance. Intraexaminer reliability was high for 11 of 12 measurements, and interexaminer reliability was high for eight of twelve. Three of the four measurements that varied between examiners were either sensory or motor amplitudes, attributes frequently used to measure disease progression or to assess the result of therapeutic intervention. Our results suggest that longitudinal nerve conduction measurements used to assess worsening or improvement over time should optimally be performed by a single examiner to minimize the degree of variability associated with different examiners.
  Neurology 09/1994; 44(8):1459-62. · 8.31 Impact Factor