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Biomedical subjects

R F White

Publications and source records attributed to R F White.

122 records · Page 7Linked to original sources

Validation of the NES2 in patients with neurologic disorders.

Performance on the Neurobehavioral Evaluation System (NES) has been demonstrated to be affected by exposure to a variety of neurotoxicants. However, the relation of NES subtests to CNS function has not yet been documented in patients diagnosed with neurologic disorders known to implicate specific brain substrates. A validation study of the NES2 was carried out in patients with multiple sclerosis (MS) and Parkinson's disease (PD), disorders exhibiting neuropathology at loci (white matter in MS, basal ganglia in PD) believed to be the sites of action of several known neurotoxicants. The results indicated that performance on certain NES2 subtests was affected in expected ways in both types of patients. However, performance on many more subtests was impaired, relative to controls, in MS than in PD. The relative insensitivity to PD suggests that expansion and refinement of the battery are required if it is to serve well in detecting the effects of toxicants in subjects without frank physical symptoms. These are the goals of a new version of the instrument currently under development (NES3).

Affect↗

A comparison of NES2 and traditional neuropsychological tests in a neurologic patient sample.

The Neurobehavioral Evaluation System (NES), a computer-assisted battery of behavioral tests, has been widely used to detect central nervous system dysfunction in occupational and environmental settings and has recently been adapted for testing of neurological patients. The purpose of the present study was to assess the relationship between NES tasks and the traditional neuropsychological tests from which many of the NES tests were developed. For this purpose, comparisons were made between scores on NES tests and traditional neuropsychological tests designed to measure functioning in the same cognitive domains in a sample of patients with idiopathic Parkinson's disease (PD). As has been found in prior studies with normal subjects, correlations between traditional and NES2 tests varied from low to moderate. Correlations tended to be low when the modality of stimulus presentation or responses was different in the NES tests from the traditional tasks (e.g., verbal rather than visual) or when divergent and highly specific cognitive functions were being measured by the tests.

Adult↗

Feasibility and validity of three computer-assisted neurobehavioral tests in 7-year-old children.

Three tests from the computerized Neurobehavioral Examination System (NES) were administered to a group of 917 Faroese children at approximately 7 years of age. The NES Continuous Performance Test (CPT) was modified to use animal silhouettes as stimuli instead of letters. Almost all children completed Finger Tapping (FT), the modified CPT, and Hand-Eye Coordination (HE). However, 18% of the children missed at least 25% of the stimuli on the CPT (full test period), and 37% of the children did not improve their HE performance by at least 10%, as compared to the first trial. Boys obtained better results than girls, and older children performed better than younger ones. However, both factors were confounded by acquaintance with computer games. Children who used glasses, who had strabismus, or who had decreased contrast sensitivity obtained less satisfactory scores, especially on CPT and HE. The NES performance was significantly associated with functional neurological performance, including catching a ball, diadochokinesia, and finger agnosia. Slight, though statistically significant, decrements were seen with increased levels of prenatal exposure to neurotoxicants, as indicated by the mercury concentrations in cord blood obtained at the time of birth. In conclusion, the tests were feasible in this age group after slight modifications, and the test results showed meaningful associations with major predictors, thus supporting the validity of the data.

Adolescent↗

Impact of contrast sensitivity performance on visually presented neurobehavioral tests in mercury-exposed children.

Presentation of neuropsychological tests on a computer screen may involve a visual challenge to the examinee. The possible need for adjustment for visual contrast sensitivity on test performance was therefore determined from data on 917 mercury-exposed children who were examined at age 7 years. Contrast sensitivity was found to be associated with performance on the computer-assisted Continuous Performance Test. However, it showed similar associations with performance on traditional pencil-and-paper tests, especially Bender Visual Motor Gestalt Test and Wechsler Intelligence Scale for Children-Revised (WISC-R) Block Designs. Contrast sensitivity was not associated with prenatal mercury exposure, and adjustment for visual function had only a negligible effect on the regression coefficients for mercury as predictor of neuropsychological deficits. The mercury-associated neurobehavioral deficits are therefore unlikely to be due to mercury-induced visual system dysfunction causing secondary deficits in cognitive domain testing. Visuospatial processing appears to be a determinant in contrast sensitivity performance, and careful consideration of whether to control for contrast sensitivity in future studies of neurotoxicant effects is therefore recommended.

Bender-Gestalt Test↗

Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants.

Prenatal exposure to polychlorinated biphenyls (PCBs) was examined by analysis of cord tissue from 435 children from a Faroese birth cohort. Analysis of 50 paired cord blood samples showed excellent correlation with the cord tissue concentration (r=.90). Among 17 neuropsychological outcomes determined at age 7 years, the cord PCB concentration was associated with deficits on the Boston Naming Test (without cues, two-tailed P=.09 not adjusted for mercury; with cues, P=.03), the Continuous Performance Test reaction time (P=.03), and, possibly, on long-term recall on the California Verbal Learning Test (P=.15). The association between cord PCB and cord-blood mercury (r=.42) suggested possible confounding. While no PCB effects were apparent in children with low mercury exposure, PCB-associated deficits within the highest tertile of mercury exposure indicated a possible interaction between the two neurotoxicants. PCB-associated increased thresholds were seen at two of eight frequencies on audiometry, but only on the left side, and no deficits occurred on evoked potentials or contrast sensitivity. The limited PCB-related neurotoxicity in this cohort appears to be affected by concomitant methylmercury exposure.

Child↗

Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury.

A cohort of 1022 consecutive singleton births was generated during 1986-1987 in the Faroe Islands. Increased methylmercury exposure from maternal consumption of pilot whale meat was indicated by mercury concentrations in cord blood and maternal hair. At approximately 7 years of age, 917 of the children underwent detailed neurobehavioral examination. Neuropsychological tests included Finger Tapping; Hand-Eye Coordination; reaction time on a Continuous Performance Test; Wechsler Intelligence Scale for Children-Revised Digit Spans, Similarities, and Block Designs; Bender Visual Motor Gestalt Test; Boston Naming Test; and California Verbal Learning Test (Children). Clinical examination and neurophysiological testing did not reveal any clear-cut mercury-related abnormalities. However, mercury-related neuropsychological dysfunctions were most pronounced in the domains of language, attention, and memory, and to a lesser extent in visuospatial and motor functions. These associations remained after adjustment for covariates and after exclusion of children with maternal hair mercury concentrations above 10 microgram(s) (50 nmol/g). The effects on brain function associated with prenatal methylmercury exposure therefore appear widespread, and early dysfunction is detectable at exposure levels currently considered safe.

Adult↗

Delayed evoked potentials in children exposed to methylmercury from seafood.

Methylmercury poisoning may cause constriction of visual fields and deafness, especially if exposure occurs prenatally. However, the risks associated with exposure from contaminated seafood is unclear. We examined 149 children attending first grade in a Madeiran fishing community. As maternal dietary habits were relatively unchanged, current maternal hair concentrations were used as indicator of the child's prenatal exposure to methylmercury (geometric average, 9.64 microg/g [48.2 nmol/g]). After adjustment for age and sex, the mean (+/-SD) latency of peak III of the brainstem auditory evoked potentials at 40 Hz was increased by 0.128+/-0.047 ms when maternal hair-mercury concentrations exceeded 10 microg/g (50 nmol/g) (p for association, 0.002), and the increase of the N145 pattern-reversal visual evoked potential latency at 15 minutes of arc was 3.16+/-1.57 ms (p for association, 0.002). No such relationships were seen with the child's own hair-mercury concentration, and other clinical examinations revealed no mercury-associated deficits. Neurophysiological evidence of adverse effects on brain function are relatively independent of confounders, and should be considered in the risk assessment of this seafood pollutant.

Child↗

Use of hydroxyethyl starch to improve granulocyte collection in the Latham blood processor.

This report describes a practical, relatively inexpensive system of leukapheresis and plateletpheresis, utilizing the Haemonetics blood processor. The results of 236 phereses of normal donors are reported, with particular attention to an evaluation of five different anticoagulant mixtures: ACD, 2 per cent citrate in saline, and three different combinations of citrate and hydroxyethyl starch (HES). These mixtures were compared with respect to their effectiveness in the harvesting of granylocytes and platelets, respectively. The best harvest of granulocytes (3.5 X 10(9) cells per liter of blood processed) was with 6 per cent HES anticoagulated with trisodium citrate. All solutions gave about the same platelet yields (a mean of 1.6 X 10(11) per liter of blood processed). Because of its higher citrate content, ACD caused three times as many donor reactions as the other solutions. The use of HES thus permits this widely available plateletpheresis system to be used for leukapheresis with only minimal procedural modification.

Anticoagulants↗

Leukapheresis of patients with chronic granulocytic leukemia (CGL), using the Haemonetics blood processor.

By the use of citrated hydroxyethyl starch (HES) as anticoagulant, the Haemonetics blood processor can be used to obtain large numbers of granulocytes from patients with CGL. This report is of 67 leukaphereses on 11 different patients. A median of 1.14 x 10(11) granulocytes was obtained per 6-cycle pheresis (3.4 x 10(10) per liter of blood processed), or eight to ten times the number obtained from comparable leukaphereses of normal donors. High yields of platelets were also obtained, although not in proportion to granulocytes, since some of the patients used as donors have normal or even low platelet counts. The patients tolerated the procedure well, and no adverse reactions to HES were observed. The patients experienced a mean 35 per cent drop in the postleukapheresis WBC count, but in no case was this drop sustained for more than a few days, and no lasting effect on the disease process was observed.

Adolescent↗

Citrate anticoagulants for plateletpheresis.

In 112 plateletphereses done by the Haemonetics blood processor, the comparative effectiveness of ACD formula A, ACD formula B, and 2 per cent citrate in saline was evaluated. With respect to yields of platelets and white blood cells (e.g., lymphocytes), ACD-B was significantly better than the other two. Both ACD-B and 2 per cent citrate gave a much lower incidence of citrate reactions in the donors than were encountered with ACD-A.

Anticoagulants↗

Modified fluid gelatin. An alternative macromolecular agent for centrifugal leukapheresis.

We studied a French modified fluid gelatin (MFG), substituting it for hydroxyethyl starch (HES) in leukapheresis procedures using three currently available blood cell separators, and observing its effects on the function of platelets and granulocytes. As a cell-collecting agent, we found MFG to be as effective as HES with intermittent flow centrifugation (Haemonetics), and slightly less so with one continuous flow device (IBM 2997). MFG was clearly less effective than HES with the Fenwal CS-3000 continuous flow separator, although we have reason to believe it would be possible to improve efficiency with this machine by changing the operating variables. Tests of platelet and granulocyte function showed negligible alteration with either agent and no difference between them. MFG disappears much more rapidly from the circulation than HES (after a single injection, it is undetectable by the third day). Reaction frequency with MFG was about the same as that of HES, with perhaps somewhat more frequent allergic manifestations.

Blood Platelets↗

Chronic neurobehavioral effects of Tokyo subway sarin poisoning in relation to posttraumatic stress disorder.

Chronic neurobehavioral effects of acute sarin poisoning were evaluated in 9 male and 9 female patients who were exposed to sarin poisoning in the Tokyo subway incident in Japan. The investigators used nine neurobehavioral tests, as well as a posttraumatic stress disorder checklist, 6-8 mo after the poisoning occurred. Serum cholinesterase activity in patients on the day of poisoning (i.e., March 20, 1995) ranged from 13 to 131 IU/l (mean=72.1 IU/l). The results of analysis covariance, in which age, education level, alcohol consumption, and smoking status (covariates) were controlled in 18 sarin cases and in 18 controls, showed that the score on the digit symbol (psychomotor performance) test was significantly lower in the sarin cases than in controls. Nonetheless, the scores for the General Health Questionnaires, fatigue of Profile of Mood States, and posttraumatic stress disorder checklist were significantly higher in the sarin cases than controls. The investigators added posttraumatic stress disorder to the covariates, and only the score on the digit symbol test was significantly lower in sarin cases. In addition, the results of stepwise multiple regression analysis in 18 sarin cases revealed that scores for the General Health Questionnaires, fatigue of Profile of Mood States (i.e., fatigue, tension-anxiety, depression, and anger-hostility)-together with the paired-associate learning test-were associated significantly with posttraumatic stress disorder. The association did not remain significant for the digit symbol test score. Perhaps a chronic effect on psychomotor performance was caused directly by acute sarin poisoning; on the other hand, the effects on psychiatric symptoms (General Health Questionnaire) and fatigue (Profile of Mood States) appeared to result from posttraumatic stress disorder induced by exposure to sarin.

Adult↗

Relationship of psychiatric status to Gulf War veterans' health problems.

OBJECTIVE: A growing body of research has shown that there are important links between certain psychiatric disorders and health symptom reporting. Two disorders in particular (posttraumatic stress disorder (PTSD) and major depression) have been the most widely implicated to date, and this association has sometimes been used to explain the occurrence of ill-defined medical problems and increased somatic symptoms in certain groups, most recently Gulf War veterans. METHODS: Structured psychiatric diagnostic interviews were used to examine the presence of major psychiatric (axis I) disorders and their relation to health symptom reporting in a well-characterized, stratified subset of Gulf War veterans and a non-Gulf-deployed veteran comparison group. RESULTS: Rates of most psychiatric disorders were substantially lower than national comorbidity estimates, consistent with prior studies showing heightened physical and emotional well-being among active-duty military personnel. Rates of PTSD and major depression, however, were significantly elevated relative to the veteran comparison group. The diagnosis of PTSD showed a small but significant association with increased health symptom reports. However, nearly two-thirds of Gulf participants reporting moderate to high health symptoms had no axis I psychiatric diagnosis. CONCLUSIONS: Results suggest that rates of psychiatric illness were generally low with the exception of PTSD and major depression. Although PTSD was associated with higher rates of reported health problems, this disorder did not entirely account for symptoms reported by participants. Factors other than psychiatric status may play a role in Gulf War health problems.

Cohort Studies↗