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Biomedical subjects

A R Potvin

Publications and source records attributed to A R Potvin.

At least 19 recordsLinked to original sources

The basis of intra-blood-brain-barrier IgG synthesis.

We hold that the intra-blood-brain-barrier (BBB) IgG synthesis (SYN) rate can be quantitated reliably and validly. Although several formulas distinguish patients with multiple sclerosis from normal controls equally well, only the SYN rate formula has been validated in humans using isotopic tracer techniques. Our formula for the IgG SYN rate is reducible to Reiber's formula; therefore, both can be used to quantify the IgG SYN rate in a manner not possible using the IgG index. Although our SYN rate formula has been validated for a modest range of BBB abnormalities (cerebrospinal fluid/serum albumin ratios), there is evidence to suggest that it may be used even in patients having severe BBB damage. We question the acceptance of unique cerebrospinal fluid IgG bands as indisputable evidence of intra-BBB IgG SYN in the presence of a modest to severely damaged BBB. Finally, the utility of quantitation and detection of intra-BBB IgG SYN by standardized methods in a group of asymptomatic, normal individuals compared with a group of patients with clinical definite multiple sclerosis is presented.

Blood-Brain Barrier

Multimodality evoked potentials and neurophysiological tests in multiple sclerosis. Effects of hyperthermia on test results.

Data on critical frequency of photic driving (CFPD), frequency following response (FFR), and visual, somatosensory (peroneal nerve), and brain-stem auditory evoked potentials (EPs) were obtained from 20 patients who had clinically definite multiple sclerosis and ten healthy normal subjects in a controlled, balanced study under normothermic and hyperthermic (+1 degrees C) conditions with a test-retest interval of one week. Normal subjects' test results showed no changes during hyperthermia. Patients' EP and CFPD data correlated well with history, clinical signs, and symptoms during both normothermia and hyperthermia. The FFR test data were equivocal and not fully analyzed. Data from the four other tests showed additional patient abnormalities during hyperthermia. Multimodality testing increased the number of patient abnormalities compared with single tests, and the number increased further during hyperthermia. Test-retest reproducibility was higher during hyperthermia.

Adult

Multiple sclerosis-specific central nervous system antigens (MSG2): a blind study.

A blinded study was designed to determine if a glycoprotein fraction, G2, shown in previous studies to be specific for multiple sclerosis (MS), could be isolated from cryopreserved autopsy central nervous system (CNS) tissue. Coded tissue sections were obtained from the Human Neurospecimen Bank, Los Angeles, Calif.; and the code was broken after all data were analyzed. Multiple sections of the CNS from 23 MS patients, 12 patients with other neurologic diseases (OND), and 10 individuals who died as a sudden death were utilized. Crossed immunoisoelectrophoresis (CIE) of G2 against anti-MS cytosol antibodies to MS-specific CNS antigens (MSG2) and tandem CIE of the G2 fraction with a known MSG2 preparation were carried out. MSG2 was found in one or more CNS sections from 78% of MS patients, all sections from MS spinal cord, and no sections from OND or control individuals. We propose that the MSG2 found in the MS CNS may contain a glycoprotein of a persistent virus, such as measles and/or myelin.

Adult

Intra-blood-brain barrier measles virus antibody synthesis in multiple sclerosis patients.

Antibodies to nine viruses were measured in serum and CSF of MS patients, patients with other neurologic diseases (OND), and healthy controls. The extent of antibody production inside the blood-brain barrier (BBB) was determined by making a new correction for BBB permeability. Compared with OND and healthy controls, MS patients as a group had significantly higher corrected CSF:serum antibody ratios for measles virus but not to the other eight viruses studied. The incidence of significantly high CSF:serum ratios for measles antibody in MS patients was 50%, and in the other two control groups it was 0 to 12%. The incidence of corrected antibody ratios to the other eight viruses was not significantly different among the three groups.

Adult

Cognition in Parkinson disease: an event-related potential perspective.

Auditory event-related potentials (ERP) elicited in a target detection stimulus paradigm and pattern-shift visual ERPs were studied in 20 male patients with idiopathic Parkinson disease (PD) and 20 age-matched normal controls. Patients showed significantly increased latencies for both the P200 and P300 components of the auditory ERP. Patients and controls showed no significant differences in latency of the visual ERP but patients showed significantly decreased amplitude. Only one of five neuropsychological measures, the Symbol Digit Modalities test (SDMT), showed a significant negative correlation with P300 latency. The significant association between the two measures that showed impairments in the PD patients (P300 latency and SDMT scores) suggested that these measures reflect a common, disrupted aspect of cognitive function in PD.

Aged

Parkinson's disease: Cogentin with Sinemet, a better response.

1. A randomized, placebo controlled, double-blind cross-over study was conducted to evaluate the clinical efficacy of the anticholinergic agent, benztropine mesylate (CogentinR) in 29 patients with mild to moderate, idiopathic Parkinson disease. 2. Patients were maintained on a stable, therapeutically optimal dosage and schedule of levadopa-carbidopa (Sinemet) throughout the study. 3. Both the neurologist's and the patient's global assessments of treatment efficacy indicated that Sinemet plus benztropine mesylate resulted in significantly greater improvement than Sinemet plus placebo. 4. Qualitative and quantitative evaluations of relevant neurologic functions showed small, but statistically significant improvements for rigidity, finger tapping speed and activities of daily living in patients during the Sinemet plus benztropine mesylate treatment period. 5. At the completion of the study 16 patients chose to continue taking benztropine mesylate as an adjuvant to Sinemet. 6. No important adverse side effects occurred during the study.

Aged

Endogenous event-related potentials: prospective applications in neuropsychology and behavioral neurology.

The primary neurologic application of event-related potentials (ERP) to date has been of relatively short-latency (less than 100-200 ms), stimulus-dependent components. These so-called exogenous components are used to evaluate the structural, and to a lesser extent, the functional integrity of primary afferent pathways. Another class of ERP, termed endogenous, and involving longer-latency (greater than 100 ms) stimulus-independent components has been utilized by psychologists and cognitive psychophysiologists in the measuring of neurocognitive processes. Although the experimental specification of these neurocognitial processes is still in its infancy, the empirical applications of endogenous ERP's offers considerable promise for objective non-invasive evaluations of cognitive functions now conducted only behaviorally. Initial neurocognitive ERP applications have focused on global mental status in dementia. A brief review is presented of experimental studies of some endogenous ERPs (mainly P300), their hypothesized underlying neurocognitive processes, and initial and potential clinical applications.

Afferent Pathways

Multiple sclerosis serum and cerebrospinal fluid immunoglobulin binding to Fc receptors of oligodendrocytes.

Suspensions of bovine oligodendrocytes were used to study the immunofluorescent staining properties of sera from multiple sclerosis (MS) patients and normal individuals. All sera (14 MS patients, 8 patients with other neurological diseases, and 11 normal individuals) showed positive oligodendrocyte staining by indirect immunofluorescence. Staining persisted after extensive absorption of sera with bovine liver to remove nonspecific binding. Similar findings were obtained for cerebrospinal fluid from all 5 MS patients as well as all 5 patients with other neurological diseases. In additional studies to determine if binding is mediated by the Fc fragment of IgG, results were: (1) ultracentrifuged normal and MS sera failed to react with oligodendrocytes, (2) positive staining with oligodendrocytes was observed after heat aggregation of IgG, (3) ox red blood cells, complexed with antibody, reacted with oligodendrocytes to produce strong rosette formation, and (4) the rosette formation could be blocked by prior treatment of oligodendrocytes with heat-aggregated IgG. The studies fail to support a previous claim for specific binding of immunoglobulins to oligodendrocytes in MS. However, they confirm and extend previous findings that the binding of IgG to oligodendrocytes may not necessarily be an antigen-antibody reaction. Therefore, adherence reactions with a putative antibody must exclude Fc-mediated binding.

Animals

Quantification of de novo central nervous system IgG measles antibody synthesis in SSPE.

De novo central nervous system (CNS) IgG measles antibody synthesis rate was determined in two patients with subacute sclerosing panencephalitis (SSPE). Cerebrospinal fluid and sera were incubated with different concentrations of measles virus to determine maximum absorption of IgG. The difference in IgG concentration before and after incubation was considered the amount of measles-specific IgG antibody. Various tests were done to assess the immunological specificity of the absorption test. Using our empirical formula, the de novo CNS IgG measles antibody synthesis rate for one patient with SSPE was 57 mg/day, or 59% of the total CNS IgG synthesis rate; for the other it was 145 mg/day, or 82%. Daily determination of CNS measles antibody by empirical formula provides a quantification of humoral immunity in SSPE that corrects for both passage of measles antibody across a damaged blood-brain barrier and the effect of an elevated blood antibody level.

Antibodies, Viral

Decreased verbal memory associated with anticholinergic treatment in Parkinson's disease patients.

The effects of chronic administration of the anticholinergic agent, benztropine mesylate (CogentinTM), on specific verbal memory were investigated as part of a placebo-controlled randomized double-blind crossover study to determine the clinical efficiency of CogentinTM as an adjuvant therapy with SinemetTM in Parkinson's disease. Twenty-nine males with clinically definite idiopathic Parkinson's disease participated in the trial. They were tested for acquisition of new word lists, and on four other cognitive tests before, during, between, and after two 10-week trial periods when they received either increasing doses of CogentinTM (maximum 2 mg) or placebo while on a maintenance dose of SinemetTM. Patients showed a statistically significant decrease (5--10%) in word list acquisition while on CogentinTM. The anticholinergic memory effect was unrelated to the degree of improved clinical efficacy of CogentinTM for the Parkinsonism, and to initial word list acquisition ability. Verbal memory findings indicate that chronic administration of an anticholinergic in even low therapeutic dosage may play an important role in memory function.

Aged

Quantitative methods in assessment of neurologic function.

Traditionally, neurologists have emphasized qualitative techniques for assessing results of clinical trials. However, in recent years qualitative evaluations have been increasingly augmented by quantitative tests for measuring neurologic functions pertaining to mental state, strength, steadiness, reactions, speed, coordination, sensation, fatigue, gait, station, and simulated activities of daily living. Quantitative tests have long been used by psychologists for evaluating asymptomatic function, assessing human information processing, and predicting proficiency in skilled tasks; however, their methodology has never been directly assessed for validity in a clinical environment. In this report, relevant contributions from the literature on asymptomatic human performance and that on clinical quantitative neurologic function are reviewed and assessed. While emphasis is focused on tests appropriate for evaluating clinical neurologic trials, evaluations of tests for reproducibility, reliability, validity, and examiner training procedures, and for effects of motivation, learning, handedness, age, and sex are also reported and interpreted. Examples of statistical strategies for data analysis, scoring systems, data reduction methods, and data display concepts are presented. Although investigative work still remains to be done, it appears that carefully selected and evaluated tests of sensory and motor function should be an essential factor for evaluating clinical trials in an objective manner.

Activities of Daily Living