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PubMed1982

Construct validity of the Weigl Color-Form Sorting Test.

This research, conducted on 38 male psychiatric inpatients, replicated previous findings that inability to "shift" conceptual attitude on the Weigl Color-Form Sorting Test is consistent with indices often associated with cortical dysfunction, such as Bender-Gestalt recall, WAIS Similarities subtest scores, and age. Regression analysis yielded a multiple R of .52, with ability to shift predictable from the difference between WAIS Verbal IQ and subjects' age. The relationship between the Weigl and the Hooper approached significance, but that between the Weigl and Trail Making did not. The Weigl might serve as a non-verbal instrument to assess cortical dysfunction where inability to "shift" appears to tap a dysfunction in symbolic reasoning rather than spatial reasoning.

Adult↗
PubMedDate not supplied

Neurobehavioral dysfunction in firemen exposed to polycholorinated biphenyls (PCBs): possible improvement after detoxification.

Fourteen firemen exposed to polychlorinated biphenyls (PCBs) and their byproducts generated in a transformer fire and explosion had neurophysiological and neuropsychological tests 6 mo after the fire. They were re-studied 6 wk later after undergoing 2-3 wk of an experimental detoxification program consisting of medically supervised diet, exercise, and sauna. A case-control comparison with firemen matched from the same department, but who did not participate in controlling the transformer fire, had shown significant impairment of memory for stories, visual images, and digits backwards. Cognitive function was impaired for block design, identifying embedded figures, and design association and recognition using Culture Fair. Making of trails and choice reaction time, which measured cognitive function and perceptual motor speed, were also impaired. These signs of protracted neurobehavioral impairment were attributed to PCBs and heat-produced byproducts. No relationship, however, was found between the firemen's serum or fat levels of PCBs as Arochlor 1248 and their type or degree of neurobehavioral impairment. Retesting following the detoxification program showed significantly improved scores on: three memory tests, block design, trails B, and embedded figures. Thus, there was significant reversibility of impairment after the detoxification interval. However self-appraisal scores for depression, anger, and fatigue--which were initially elevated--and for vigor--which was reduced--did not change across this interval.

Adult↗
PubMed2002

ApoE genotype, past adult lead exposure, and neurobehavioral function.

Our objective in this study was to determine if the known relation between tibia bone lead levels and neurobehavioral test scores are influenced by the apolipoprotein E (ApoE) genotype. We collected data on 20 neurobehavioral tests in 529 former organolead workers who had an average of 16 years since last occupational exposure to lead. We used linear regression to model the relations between each of 20 neurobehavioral test scores and tibia lead, a binary variable for ApoE genotype (i.e., at least one Epsilon4 allele vs. none), and an interaction term between tibia lead and the binary term for ApoE genotype. At the time of testing, former lead workers were an average of 57.6 years of age; 82% were younger than 65 years. In regression analysis, we observed one statistically significant and one borderline significant coefficient for ApoE genotype alone. Coefficients for the ApoE and tibia lead interaction term were negative in 19 of the 20 regression models. This indicates that the slope for the relation between tibia lead and each neurobehavioral test was more negative for individuals with at least one Epsilon4 allele than for those who did not have an Epsilon4 allele. Four of 19 negative coefficients for the interaction term were statistically significant (digit symbol, Purdue pegboard assembly, Purdue pegboard-dominant hand, complex reaction time); another three of the remaining 16 coefficients (symbol digit, trail-making A, Stroop) were borderline significant (i.e., p < 0.10). This study suggests that individuals may vary in susceptibility to the long-term effects of lead on the central nervous system (CNS). In particular, the persistent CNS effect of lead may be more toxic in individuals who have at least one ApoE-Epsilon4 allele.

Adult↗
PubMedDate not supplied

Effects of 5-isosorbide mononitrate and propranolol on subclinical hepatic encephalopathy and renal function in patients with liver cirrhosis.

BACKGROUND/AIMS: In patients with cirrhosis pharmacological treatment of portal hypertension using beta-blockers and vasodilators has raised concerns for its potential deleterious effects on renal function and encephalopathy. To clarify this issue we evaluated the effects of propranolol and 5-isosorbide mononitrate or both on subclinical hepatic encephalopathy and renal function in a prospective randomized double-blinded study. METHODOLOGY: Thirty patients Child-Pugh A or B, with esophageal varices, normal renal function and non-previous pharmacological treatment were studied. After a basal period, patients received during 4 weeks 5-isosorbide mononitrate (80 mg/day) or placebo. In the next 4 weeks, propranolol was added to both groups. At baseline and at the end of each study period we assessed: renal function tests; plasma renin activity and aldosterone; subclinical hepatic encephalopathy (electroencephalograms, visual evoked potentials and psychometric studies). Mean arterial pressure, cardiac output (echo-Doppler) and indocyanine green retention were also measured. RESULTS: The most common alterations at baseline were increased arterial ammonia levels (85%), abnormal indocyanine green retention (75%), abnormal trail making B (44%), decreased inulin clearance (30%) and high plasma renin activity (27%). After 4 weeks of 5-isosorbide mononitrate or placebo no significant changes were observed in any variable. Five out of 14 patients receiving 5-isosorbide mononitrate were withdrawn due to side effects. The addition of propranolol decreased significantly plasma renin activity in both groups and cardiac output in those receiving 5-isosorbide mononitrate but did not change other variables. CONCLUSIONS: In patients with compensated or slightly decompensated liver cirrhosis 5-isosorbide mononitrate, propranolol or the association of both did not produce detectable worsening of subclinical hepatic encephalopathy or renal function.

Aged↗
PubMed1980

The training of clinical trails statisticians: a clinician's view.

Clinical investigations today involves not only multidisciplinary teamwork but also investigators at multiple institutions observing the same criteria and standards in order to make possible the valid pooling of data in collaborative studies. As a result, there has been increasing awareness of the biostatistician's role, not simply in interpreting the data at the end of the study, but in every step of clinical investigation. This involvement ranges from study design and feasibility testing to data analysis and reporting. The problem is now a shortage of biostatisticians appropriately trained for clinical trials statistical methodology. As the statistician's role is of great importance, more graduate training programs in statistics should prepare statisticians for clinical trials work. This would pave the way to the many exciting and rewarding career opportunities which are available for statisticians in the area of clinical trails.

Career Choice↗
PubMed1998

The WAIS-R factors: usefulness and construct validity in neuropsychological assessments.

One-hundred and twelve patients were administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R), an abbreviated Wechsler Memory Scale-Revised, and the Halstead-Reitan Neuropsychological Test Battery. In order to replicate an earlier study (Sherman, Strauss, Spellacy, & Hunter, 1995), correlations were generated between the WAIS-R factor scores and neuropsychological and memory tests. The Verbal Comprehension factor (Factor 1) correlated with Speech Sounds Perception Test (SSPT), the Seashore Rhythm Test (SSRT), the Category Test, and memory indices. The Perceptual Organizational factor (Factor 2) correlated with the time, memory, and location scores of the Tactual Performance Test, the SSPT, SSRT, the Category Test, Trails A, Trails B, memory indices, and finger tapping. The Freedom From Distractibility factor (Factor 3) was correlated with the Category Test, the SSPT, the SSRT, Trails A, Trails B, immediate Logical Memory, and Visual Reproduction. Modest correlations suggest that the WAIS-R factors may be useful for understanding underlying cognitive performance and can be functional for generating hypotheses, but should not be utilized exclusively to make clinical inferences.

Journal Article↗
PubMed2004

Is a "loss of balance" a control error signal anomaly? Evidence for three-sigma failure detection in young adults.

Given that a physical definition for a loss of balance (LOB) is lacking, the hypothesis was tested that a LOB is actually a loss of effective control, as evidenced by a control error signal anomaly (CEA). A model-reference adaptive controller and failure-detection algorithm were used to represent central nervous system decision-making based on input and output signals obtained during a challenging whole-body planar balancing task. Control error was defined as the residual generated when the actual system output is compared with the predicted output of the simple first-order polynomial system model. A CEA was hypothesized to occur when the model-generated control error signal exceeded three standard deviations (3sigma) beyond the mean calculated across a 2-s trailing window. The primary hypothesis tested was that a CEA is indeed observable in 20 healthy young adults (ten women) performing the following experiment. Seated subjects were asked to balance a high-backed chair for as long as possible over its rear legs. Each subject performed ten trials. The ground reaction force under the dominant foot, which constituted the sole input to the system, was measured using a two-axis load cell. Angular acceleration of the chair represented the one degree-of-freedom system output. The results showed that the 3sigma algorithm detected a CEA in 94% of 197 trials. A secondary hypothesis was supported in that a CEA was followed in 93% of the trials by an observable compensatory response, occurring at least 100 ms later, and an average of 479 ms, later. Longer reaction times were associated with low velocities at CEA, and vice versa. It is noteworthy that this method of detecting CEA does not rely on an external positional or angular reference, or knowledge of the location of the system's center of mass.

Adolescent↗
PubMedDate not supplied

Chlorine-induced damage documented by neurophysiological, neuropsychological, and pulmonary testing.

Chlorine causes acute pulmonary edema and damages airways, thus producing obliterative bronchiolitis. In the case series in this study, its adverse effects were extended to visual and central nervous system impairment. Twenty-two patients exposed briefly to undiluted chlorine at home or work were evaluated with a battery of neurobehavioral and visual tests. Their test scores, expressed as percentage predicted, were compared with those of unexposed subjects. Chlorine-exposed subjects had impaired balance (with eyes open and eyes closed), delayed simple and choice reaction times, impaired color discrimination, impaired visual field performance, decreased hearing, and decreased grip strength. Blink reflex latency was delayed on the right. Cognitive performance (i.e., digit symbol and vocabulary), peg placement, trail making A and B, and verbal recall were significantly below predicted levels. Well-learned memory functions were not impaired. Adverse mood states scores were elevated as were the frequencies of 28 of 35 common symptoms. Forced vital capacities were reduced. The duration of chlorine exposures was from a breath or two to several hours, and exposures were associated with impaired neurophysiologic and neuropsychologic functions. Impairments appeared insidiously, were noted 1 to 48 mo after exposure, and persisted. Such functional losses must be prevented. Additional chlorine-exposed patients should be evaluated for neurological and pulmonary damage.

Adult↗
PubMed1995

[Benign prostatic hypertrophy. Optimized diagnosis].

The optimal diagnostics of B.P.H. must be efficient, cheap and of spare invasiveness either physical than psychological. The optimization of diagnosis is the obtainment of high quality in the services provided, matched to a correct and shrewd utilisation of resources. To optimise a diagnosis efficiency is necessary, which means the largest degree of standardization of diagnostical procedures, with responsible management of economical factors. A course of standardization, cause his excessive simplification, cannot shared to a lot of Urologists, because in their opinion there is a risk to lose informations in every single patient, but is essential to use a universal language that make easy the comparison with patients and with results whether in order to clinics or trails. The standardisation of diagnostics consists to obtain the maximum of informations from present methodology and that is possible to realize in two way: improving the technique of execution and including the diagnostic test in the appropriate point of algorithm.

Age Factors↗
PubMed1998

Epidemiological association in US veterans between Gulf War illness and exposures to anticholinesterases.

To investigate complaints of Gulf War veterans, epidemiologic, case-control and animal modeling studies were performed. Looking for OPIDP variants, our epidemiologic project studied 249 Naval Reserve construction battalion (CB24) men. Extensive surveys were drawn for symptoms and exposures. An existing test (PAI) was used for neuropsychologic. Using FACTOR, LOGISTIC and FREQ in 6.07 SAS, symptom clusters were sought with high eigenvalues from orthogonally rotated two-stage factor analysis. After factor loadings and Kaiser measure for sampling adequacy (0.82), three major and three minor symptom clusters were identified. Internally consistent by Cronbach's coefficient, these were labeled syndromes: (1) impaired cognition; (2) confusion-ataxia; (3) arthro-myo-neuropathy; (4) phobia-apraxia; (5) fever-adenopathy; and (6) weakness-incontinence. Syndrome variants identified 63 patients (63/249, 25%) with 91 syndromes. With pyridostigmine bromide as the drug in these drug-chemical exposures, syndrome chemicals were: (1) pesticide-containing flea and tick collars (P < 0.001); (2) alarms from chemical weapons attacks (P < 0.001), being in a sector later found to have nerve agent exposure (P < 0.04); and (3) insect repellent (DEET) (P < 0.001). From CB24, 23 cases, 10 deployed and 10 non-deployed controls were studied. Auditory evoked potentials showed dysfunction (P < 0.02), nystagmic velocity on rotation testing, asymmetry on saccadic velocity (P < 0.04), somatosensory evoked potentials both sides (right P < 0.03, left P < 0.005) and synstagmic velocity after caloric stimulation bilaterally (P-range, 0.02-0.04). Brain dysfunction was shown on the Halstead Impairment Index (P < 0.01), General Neuropsychological Deficit Scale (P < 0.03) and Trail Making part B (P < 0.03). Butylcholinesterase phenotypes did not trend for inherent abnormalities. Parallel hen studies at Duke University established similar drug-chemical delayed neurotoxicity. These investigations lend credibility that sublethal exposures to drug-chemical combinations caused delayed-onset neurotoxic variants.

Case-Control Studies↗
PubMed2003

Brain but not lung functions impaired after a chlorine incident.

A workplace bleach exposure incident was studied in 13 women to determine whether chlorine caused neurobehavioral and pulmonary functional effects. We compared neurophysiological and neuropsychological measurements in 13 chlorine-exposed women, 4.5 years after exposure, and 41 unexposed women. Reaction times, balance, blink reflex latency, color discrimination and several psychological tests were measured. Pulmonary function was assessed by spirometry. A profile of mood states and frequencies of 35 symptoms were obtained. Chlorine exposed women performed statistically significantly below unexposed women for simple and choice reaction times, balance with eyes open and eyes closed, color discrimination, grip strength, Culture Fair, digit symbol substitution, vocabulary, trail making B and pegboard. Profile of mood states scores and frequency symptoms were elevated. Respiratory symptoms were elevated but pulmonary volumes and flows were not reduced. Chlorine bleach exposure was associated with impaired neurobehavioral functions and elevated POMS scores and symptom frequencies. Alternatives to chlorine should be used.

Administration, Cutaneous↗
PubMedDate not supplied

Improving medical imaging report turnaround times: the role of technolgy.

At Southern Ohio Medical Center (SOMC), the medical imaging department and the radiologists expressed a strong desire to improve workflow. The improved workflow was a major motivating factor toward implementing a new RIS and speech recognition technology. The need to monitor workflow in a real-time fashion and to evaluate productivity and resources necessitated that a new solution be found. A decision was made to roll out both the new RIS product and speech recognition to maximize the resources to interface and implement the new solution. Prior to implementation of the new RIS, the medical imaging department operated in a conventional electronic-order-entry to paper request manner. The paper request followed the study through exam completion to the radiologist. SOMC entered into a contract with its PACS vendor to participate in beta testing and clinical trials for a new RIS product for the US market. Backup plans were created in the event the product failed to function as planned--either during the beta testing period or during clinical trails. The last piece of the technology puzzle to improve report turnaround time was voice recognition technology. Speech recognition enhanced the RIS technology as soon as it was implemented. The results show that the project has been a success. The new RIS, combined with speech recognition and the PACS, makes for a very effective solution to patient, exam, and results management in the medical imaging department.

Contract Services↗
PubMedDate not supplied

Neurotoxic effects from residential exposure to chemicals from an oil reprocessing facility and superfund site.

Neurotoxicity has been described in workers exposed to solvents, PCBs, certain metals, and polyaromatic hydrocarbons but not often in residents near refineries or factories. We compared the neurobehavioral performance of residents near a plant that reprocessed used motor oil and chemical waste from 1966-1983 to referents from beyond the plant's modeled air dispersal and water drainage zones. Neurophysiological and psychological tests, a Profile of Mood States (POMS) and a symptom questionnaire were administered to 131 subjects exposed at the site who were matched for age, sex, and ethnicity 2:1 with 66 unexposed subjects from 35 km away. Test scores were adjusted for a 1.4-year difference in educational attainment by coefficients from regression equations but not for income as the latter coefficients were not significant. Exposed subjects were significantly impaired for body balance (sway speed) and simple and two choice visual reaction time as compared to referents. Blink reflex latency (R-1) and eye closure speed were normal in both groups. Cognitive function in the exposed was impaired as measured by Culture Fair and by block design from the WAIS. Placing pegs in a grooved board and making of trails (A and B) were also impaired. Group differences in recall and memory were not significant. The exposed group's symptom frequencies and POMS scores for depression, anger, confusion, tension, and fatigue were elevated indicating depression. Confounding from medical and neurological disorders or occupational exposures was minimal. Subjects exposed residentially for up to 17 years to chemicals dispersed from a waste oil reprocessing plant showed neurophysiological and neuropsychological impairment.

Adolescent↗
PubMedDate not supplied

Neurobehavioral impairment and symptoms associated with aluminum remelting.

The author's objective was to assess whether aluminum reclamation (recycling) exposure in a plant in the southeastern United States was associated with neurobehavioral and pulmonary impairment and symptoms. The author made cross-sectional comparisons of 41 workers to 32 local and 66 regional referents to assess whether aluminum recycling was associated with neurobehavioral and pulmonary impairment and symptoms. Methods included neurophysiological, psychological, and pulmonary-function tests; a Profile of Mood States (POMS); and questionnaires. The exposed subjects had slower simple and choice reaction times than referents (i.e., 77 milliseconds [ms] versus 137 ms, respectively [p < .0001]); balance in the exposed subjects, measured as sway speed (with eyes closed), was .32 cm/s faster than for referents (p < .005); and color discrimination was less acute in exposed subjects (p < .0001). In the exposed versus referent subjects, Culture Fair scores were lower by a factor of 8.3 (p < .0001), Trail Making A was 10 s longer (p < .001), Trail Making B was 50 s longer (p < .0001), peg placement required an additional 9 s (p < .008), and POMS scores were fourfold higher (p < .0001). These described differences were not explained by age, bias, or confounding factors. Workers had more neurobehavioral, rheumatic, and respiratory symptoms than did referents. The author attributed the differences between the two groups to chemical exposures from aluminum remelting, including aluminum, manganese, vinyl chloride monomer, and other chemicals. Workplace air could not be sampled, but because a problem was identified, levels of these, as well as other chemicals, should be measured in future studies.

Adolescent↗
PubMed1996

The Edinburgh cohort of HIV-positive injecting drug users at 10 years after infection: a case-control study of the evolution of dementia.

OBJECTIVE: To examine the evolution of dementia in HIV-positive injecting drug users (IDU) in Edinburgh. DESIGN: Case-control study. PARTICIPANTS: Twenty six (6%) out of 404 patients in the Edinburgh cohort of HIV-positive IDU who have developed HIV-1-associated dementia in the 10 years since infection and seroconversion. METHODS: Patients were tested repeatedly, where possible, on a range of neuropsychological and neurophysiological measures. The results from patients with dementia were compared with those of age, sex and IQ-matched non-demented HIV-positive controls from the cohort. An auditory event-related potential (P3 or P300), a neurophysiological measure of cognitive function, detected the onset of a marked slowing of cognitive and psychomotor functions. Neuropsychological measures that involve the speed of information processing such as the Trail-Making task also identified the early stages of dementia. RESULTS: Dementia was associated with a more advanced stage of systemic disease, increased rates of decline in CD4 cell counts and markedly reduced survival compared with the non-demented controls. No evidence for a protective effect of treatment with zidovudine was detected. CONCLUSION: In the first 10 years after infection with HIV-1 dementia is an individual development, not the clinical extreme of general intellectual impairment, and had occurred in at least 6% of our IDU cohort. Future questions concern the long-term rate of dementia, the critical neuropathological change and the true potential for early treatment.

AIDS Dementia Complex↗
PubMed2007

Pharmacodynamic biomarkers for molecular cancer therapeutics.

Rational and efficient development of new molecular cancer therapeutics requires discovery, validation, and implementation of informative biomarkers. Measurement of molecular target status, pharmacokinetic (PK) parameters of drug exposure, and pharmacodynamic (PD) endpoints of drug effects on target, pathway, and downstream biological processes are extremely important. These can be linked to therapeutic effects in what we term a "pharmacological audit trail." Using biomarkers in preclinical drug discovery and development facilitates optimization of PK, PD, and therapeutic properties so that the best agent is selected for clinical evaluation. Applying biomarkers in early clinical trials helps identify the most appropriate patients; provides proof of concept for target modulation; helps test the underlying hypothesis; informs the rational selection of dose and schedule; aids decision making, including key go/no go questions; and may explain or predict clinical outcomes. Despite many successes such as trastuzumab and imatinib, exemplifying the value of targeting specific cancer defects, only 5% of oncology drugs that enter the clinic make it to marketing approval. Use of biomarkers should reduce this high level of attrition and bring forward key decisions (e.g., "fail fast"), thereby reducing the spiraling costs of drug development and increasing the likelihood of getting innovative and active drugs to cancer patients. In this chapter, we focus primarily on PD endpoints that demonstrate target modulation, including both invasive molecular assays and functional imaging technology. We also discuss related clinical trial design issues. Implementation of biomarkers in trials remains disappointingly low and we emphasize the need for greater cooperation between various stakeholders to improve this.

Animals↗
PubMed2001

Neuropsychological sequelae of 50 Hz magnetic fields.

PURPOSE: The effects of occupational levels of 50 Hz magnetic fields on cognitive function were studied on 30 human volunteers. MATERIALS AND METHODS: The exposure system consisted of Merrit-type modified Helmholtz coils forming a 2 m cube, employing two orthogonal sets of coils producing a 28 microT (resultant) circularly polarized 50 Hz magnetic field. Subjects sat at a desk within the coils where they undertook a series of verbal and written tests of cognitive function. After these tests were concluded (approximately 30 min) subjects were either exposed or sham-exposed to fields (double-blinded) for 50 min. A second set of tests (employing alternate versions) was administered 20 min from the start of this period. Each subject returned after 7 days to repeat the sequence, but with the opposite field/sham status. RESULTS AND CONCLUSIONS: The majority of the results indicated no significant effect of exposure on cognition. However, verbal recall of a list of 15 words after an interference (the different list) was significantly impaired in the 'field on' condition. This is indicative of a reduction in short-term memory of words. The mean baseline score was somewhat higher in the 'field on' condition. However, this difference is within the parameters of normal variation. The other significant result occurred during performance of a trail-making task (alternating 1-A-2-B-3-C, etc.), with a decrease in performance as a result of exposure to the 50 Hz field. This task requires executive functioning with a working memory load, involving parietal spatial processing coordinated by prefrontal executive processing. In summary, the data are suggestive of detrimental effects on cognitive processes, particularly short-term learning and executive functioning. However, larger sample sizes are required to demonstrate statistically a more specific pattern of cognitive effects.

Adult↗
PubMed1985

Regional cortical dysfunction in schizophrenic patients studied by computerized neuropsychological methods.

18 RDC-diagnosed schizophrenic patients (11 men, 7 women) were compared to 84 normal men with three computerized neuropsychological methods, assumed to reflect lateralized and frontal cortical functions: (1) Bilateral Finger Tapping and Finger Alternation, (2) Bilateral Trail Making, and (3) passively perceived Necker cube reversals. Schizophrenics differed from normals by (1) inferior Tapping/Alternation but only in the right hand, (2) inferior Trail Making, most pronounced for Form B, and (3) lower frequency of Necker cube reversals. Patients with previous neuroleptic medication and prior psychiatric hospitalizations were inferior in Trail Making and had fewer Necker cube reversals. The findings were interpreted in line with recent models of schizophrenia involving a left-hemisphere dysfunction/over-activation and a frontal dysfunction.

Adult↗