Does P3 reflect attentional or memory performances, or cognition more generally?

The study evaluated the off-line relationship of attention, memory and other cognitive performances with the auditory event-related potentials P3 (P300) and N2. The sample comprised 200 middle-aged construction workers. Verbal, visuomotor and memory tests were administered. Attentional domains were examined using CogniSpeed software. Slowed reaction times in the test of sustained attention (vigilance) were associated with delayed P3 latency (p < 0.001) and decreased P3 amplitude (p = 0.005), as well as with delayed N2 latency (p < 0.001). Visuomotor slowing in Digit Symbol was also related to delayed P3 latency (p = 0.030) and decreased P3 amplitude (p = 0.014). In contrast, mild cognitive impairment, short- and long-term memory, and concentrating or sharing attention with high working memory demands were not related to P3. The results suggest that P3 is linked to attentional performance with low working memory demands rather than to effortful working memory updating, retrieval from memory stores, or mild cognitive impairment.

Predictors and consequences of unemployment among construction workers: prospective cohort study.

OBJECTIVE: To study predictors and consequences of unemployment. DESIGN: Prospective cohort study. SETTING: 11 construction companies in southern Finland. PARTICIPANTS: 586 male employees, aged 40-59 years at baseline in 1991 and not retired during a 4 year follow up. MAIN OUTCOME MEASURES: Long term unemployment, stress symptoms, disease, alcohol consumption, exercise activity, and body mass index. RESULTS: In a multiple logistic regression model, long term unemployment (>24 months v

Risk factors for mortality in Type II (non-insulin-dependent) diabetes: evidence of a role for neuropathy and a protective effect of HLA-DR4.

To test the hypothesis that interaction between genetic, immunological, clinical and metabolic risk factors influences the outcome of Type II (non-insulin-dependent) diabetes mellitus, we examined which of the above factors present at baseline were associated with mortality in 134 Type II diabetic patients followed for 9 years. Thirty-eight patients (29%) died during the follow-up period; the majority of whom (68%) died from cardiovascular disease. At baseline, the deceased patients had higher HbA1c values (p = 0.002), higher LDL-triglycerides (p = 0.007), lower HDL-cholesterol (p = 0.007), higher non-esterified fatty acid (NEFA) concentrations (p = 0.014), and higher albumin excretion rate (p < 0.0001) than the patients who survived. In addition, the frequency of HLA-DR4 (21 vs 39%, p = 0.048) and of parietal cell antibodies (5 vs 14%, p = 0.016) were decreased in the deceased as compared to the living patients. Patients who died during follow-up also had more retinopathy (42 vs 16%, p = 0.002), neuropathy (57 vs 23%, p < 0.001), microalbuminuria (45 vs 6%, p < 0.0001), coronary heart disease (50 vs 13%, p < 0.0001), and peripheral vascular disease (27 vs 9%, p = 0.005) at baseline than patients who survived. In a multiple logistic regression analysis macroangiopathy (p = 0.004), neuropathy (p = 0.007), HbA1c (p = 0.018) and albumin excretion rate (p = 0.016) were independent risk factors for death. In patients free of cardiovascular disease at baseline, conventional risk factors such as LDL-cholesterol (p = 0.005) and age (p = 0.003) were associated with subsequent development of cardiovascular disease. In conclusion, in addition to coexisting macroangiopathy, increased albumin excretion rate, poor glycaemic control and neuropathy are risk factors for cardiovascular mortality in patients with Type II diabetes. The presence of HLA-DR4 and signs of autoimmunity may be associated with decreased risk of cardiovascular disease.

Occupational exposure to lead and neuropsychological dysfunction.

OBJECTIVE: To evaluate the neuropsychological effects of current low level and previous higher levels of exposure to lead and evaluate the relation between effects of lead and bone lead. METHODS: A neuropsychological test battery was given to 54 storage battery workers with well documented long term exposure to lead. The effect was studied in two subgroups: those whose blood lead had never exceeded 2.4 mmol/l (the low BPbmax group, n = 26), and those with higher exposure about 10 years earlier (the high BPbmax group, n = 28). In both groups, the recent exposure had been low. Correlations between the test scores and the indices of both long term and recent exposure--including the content of lead in the tibial and calcaneal bone--and covariance analyses were used to assess the exposure-effect relation. Age, sex, and education were controlled in these analyses. RESULTS: Analyses within the low BPbmax group showed a decrement in visuospatial and visuomotor function (block design, memory for design, Santa Ana dexterity), attention (digit symbol, digit span), and verbal comprehension (similarities) associated with exposure to lead and also an increased reporting of subjective symptoms. The performance of the high BPbmax group was worse than that of the low BPbmax group for digit symbol, memory for design, and embedded figures, but there was no reporting of symptoms related to exposure, probably due to selection in this group. No relation was found between the output variables and the tibial lead concentration. The calcaneal lead concentrations were related to the symptoms in the low BPbmax group. CONCLUSIONS: Neuropsychological decrements found in subjects with high past and low present exposure indicate that blood lead concentrations rising to 2.5-4.9 mmol/l cause a risk of long lasting or even permanent impairment of central nervous system function. Milder and narrower effects are associated with lower exposures; their reversibility and time course remain to be investigated. History of blood lead gives a more accurate prediction of the neuropsychological effects of lead than do measurements of bone lead.

Effects of low level exposure to lead on neurophysiological functions among lead battery workers.

OBJECTIVES: Assessment of neurophysiological functions in workers with low level exposure to lead and evaluation of the efficacy of bone lead measurements in the prediction of effects of lead. METHODS: Exposure to lead of 60 workers from a lead battery battery factory was estimated from historical blood lead measurements and analysis of lead in the tibial and calcaneal bones with x ray fluorescence. Peripheral and central nervous system functions were assessed by measuring conduction velocities, sensory distal latencies, sensory amplitudes, and vibration thresholds as well as by quantitative measurement of the absolute and relative powers and mean frequencies of different electroencephalograph (EEG) channels. RESULTS: Sensory amplitudes, and to a smaller degree sensory or motor conduction velocities, showed a negative correlation with long term exposure to lead, most clearly with integrated blood lead concentration and exposure time. Vibration thresholds measured in the arm were related to recent exposure to lead, those measured in the leg to long term exposure. The alpha and beta activities of the EEG were more abundant in subjects with higher long term exposure to lead. Calcaneal lead content reflected short term exposure, tibial lead content reflected long term exposure. Blood lead history showed a closer relation with effects of lead than the tibial or calcaneal lead concentrations. CONCLUSIONS: Vibratory thresholds, quantitative EEG, and to a smaller extent the sensory amplitude, provide sensitive measures of effects of lead in occupationally exposed adults. Most accurate estimates of health risks induced by lead can be obtained from a good history of blood lead measurements. If such a history of blood lead concentrations is not available, analysis of bone lead may be used for the assessment of health risks.

Driving ability in cancer patients receiving long-term morphine analgesia.

When given in single doses to healthy volunteers, opioid analgesics impair reaction time, muscle coordination, attention, and short-term memory sufficiently to affect driving and other skilled activities. Despite the increasing use of oral morphine daily, little is known about the effect of long-term opioid therapy on psychomotor performance. To examine the effects of continuous morphine medication, psychological and neurological tests originally designed for professional motor vehicle drivers were conducted in two groups of cancer patients who were similar apart from experience of pain. 24 were on continuous morphine (mean 209 mg oral morphine daily) for cancer pain; and 25 were pain-free without regular analgesics. Though the results were a little worse in the patients taking morphine, there were no significant differences between the groups in intelligence, vigilance, concentration, fluency of motor reactions, or division of attention. Of the neural function tests, reaction times (auditory, visual, associative), thermal discrimination, and body sway with eyes open were similar in the two groups; only balancing ability with closed eyes was worse in the morphine group. These results indicate that, in cancer patients receiving long-term morphine treatment with stable doses, morphine has only a slight and selective effect on functions related to driving.

Autonomic nervous system and cardiac involvement in familial amyloidosis, Finnish type (FAF).

Familial amyloidosis, Finnish type (FAF), is a gelsolin-related inherited systemic amyloidosis. We report autonomic nervous system and cardiac findings in a study of 30 FAF patients (18 females, 12 males aged 27-74 years; mean 53.9 years). Cardiovascular reflex tests showed a significant decrease in heart rate variation in FAF patients compared with healthy controls. Orthostatic hypotension was found in 9 of 28 FAF patients, but only in 3 of 69 controls. Signs of amyloid cardiopathy were rare at clinical examination and in radio-, echocardio- and electrocardiographic examinations. Histological and immunohistochemical studies revealed amyloid deposition and immunoreactivity against the gelsolin-related FAF amyloid subunit in autonomic nervous system structures and in cardiac tissue in 3 autopsied FAF patients. The results show that minor autonomic nervous system dysfunction can be found in FAF, while clinically significant amyloid cardiopathy or autonomic neuropathy is not characteristic of this type of amyloidosis.

Autonomic nervous system function in narcolepsy.

A disturbance of the autonomic nervous system (ANS) in narcolepsy has been suggested, based on abnormalities on pupillometry, ejaculatory and cardiovascular function. The ANS function was studied by measuring the variation in the heart rate and blood pressure during provocations, using the following tests: deep breathing test, Valsalva test and Orthostatic test for heart rate reactivity measurements, and Orthostatic test for blood pressure control. Each test session gave seven variables, and these were compared to age-adjusted reference values in healthy normals. In 22 unmedicated narcoleptics (median age 50.5 y, range 18-70 y) the results did not differ from these. Seventeen of the patients were included in a controlled stimulant medication trial (selegiline 10-40 mg daily), and they showed no significant changes in the ANS variables except for a dose-dependent rise in heart ratio (placebo 1.32+/-1-0.13 and 40 mg 1.14+/-0.05; mean+/-SD) and a decrease in systolic blood pressure (placebo 5.8+/-9.7 and 40 mg 30.1+/-21.5 mmHg) on Orthostatic test. Although blood pressure decreases >/=30 mmHg (maximally 72 mmHg) occurred in 9 patients, they were asymptomatic. These changes are considered primarily to reflect the known characteristic of monoamine oxidase inhibitors to cause postural hypotonia. Abnormalities using these methods were not found, thus supporting the view that cardiovascular reflex abnormalities would be characteristic of narcolepsy.

Internal load of aluminum and the central nervous system function of aluminum welders.

OBJECTIVES: Because the brain is the recognized target organ for aluminum toxicity, internal aluminum load and central nervous system functions were investigated among aluminum welders in a shipyard. METHODS: Seventeen male welders with a mean age of 37 (range 24-48) years and a history of about four years of metal inert-gas welding on aluminum were the subjects. Aluminum in serum (S-Al) and urine (U-Al) was analyzed with graphite-furnace atomic absorption spectrophotometry. Central nervous system functions were examined with neuropsychological tests, symptom and mood questionnaires, quantitative electroencephalography (QEEG), and P300 evoked responses. RESULTS: The mean S-Al concentration was 0.21 (range 0.03-0.64) mumol.l-1 and the mean U-Al was 2.8 (range 0.9-6.1) mumol.l-1. Although the welders performed normally on the neuropsychological tests, there was a negative association between all four memory tests and U-Al and a positive association between the variability of visual reaction times and S-Al. In the QEEG, the amount of delta and theta activity in the frontal region correlated positively and the amount of alpha activity in the frontal region correlated negatively with S-Al. CONCLUSIONS: The S-Al and U-Al measurements indicated increased internal loads of aluminum in most of the welders. This finding is compatible with slowly eliminated aluminum from tissues. The neuropsychological assessment suggested disturbing effects of aluminum on short-term memory, learning, and attention. In the QEEG, a corresponding exposure-effect relationship was found for activity in the frontal region. Further studies are needed on the possibility that exposure to aluminum welding fumes causes harm to human health.

Methodological approach to the evaluation of neurotoxicity data and the classification of neurotoxic chemicals.

This text is the result of the authors' involvement in a working group on criteria for the identification and classification of neurotoxic chemicals. (The work of the group does not necessarily represent the official stand of the affiliated institutes.) A definition of neurotoxicity and criteria for evaluating studies dealing with neurotoxicology are presented. The evaluation is a stepwise process that ends with assigning the chemicals to groups depending on the available evidence for neurotoxicity (ie, neurotoxic, probably neurotoxic, possibly neurotoxic, probably not neurotoxic, or not classifiable). Finally, the description of the potency of neurotoxic chemicals is briefly discussed. The model has been tested by evaluating selected research papers on the following 10 chemicals: manganese, aluminum, tetrahydrofuran, cyclohexanone, dichlorvos, trichloroethylene, formaldehyde, tri-ortho-cresyl phosphate, n-hexane, and vinyl chloride. There was sufficient evidence for classifying five of the ten chemicals (aluminum, manganese, n-hexane, trichloroethylene, tri-ortho-cresyl phosphate) as definitely neurotoxic to humans, and three were considered to be possibly neurotoxic to humans (dichlorvos, tetrahydrofuran, vinyl chloride). Cyclohexanone and formaldehyde were not classifiable according to the model.

Effects of recombinant alpha-2b-interferon therapy in patients with progressive MS.

The effects of systemic recombinant interferon-alpha-2b were studied in 6 carefully selected patients with progressive multiple sclerosis. 3.0 million IU were given as daily subcutaneous injections for 6 months, 5 patients showed worsening disability, and in 4 of them new or enlarged lesions were detected in MRI. In one patient no change in disability was found; his MRI showed regressed changes. The mean progression index during the treatment was significantly higher (p < 0.02) than during the previous 2 to 3 years' period of continuous progression. The frequency of peripheral blood natural killer (CD16+) cells declined significantly 3 months during the treatment, but returned to the pretreatment values after termination the treatment. An increase of intrathecal IgG synthesis and oligoclonal bands was demonstrated in 4 and 3 patients, respectively. Our experience suggests that long-term recombinant IFN-alpha-2b treatment may activate the immunological process of MS.

Nervous system effects of occupational exposure to styrene: a clinical and neurophysiological study.

Quantitative EEG of 99 workers occupationally exposed to styrene was analyzed and compared to exposure parameters. All of the workers came from reinforced plastics industry. The workplaces and factories were previously evaluated, and the exposure levels were known rather accurately. The exposure information form workplaces and the individual exposure data were combined to form an Exposure Index, which reliably reflected long-term exposure to styrene in various occupational settings. All of the subjects underwent careful medical, neurological, and neurophysiological examinations. Quantitative EEG was recorded from 19 channels and analyzed for absolute and relative power, asymmetry, coherence, frequency distribution, and statistical normative database comparisons (Neurometrics). The EEG data showed a significant increase of abnormal EEG classifications in workers with higher exposure. When the workers were divided into two groups, based on the exposure data, those with higher exposure had higher absolute EEG power in alpha and beta bands in the frontotemporal regions of the brain. The findings indicate that abnormalities in cerebral function can be demonstrated even with relatively low mean exposure levels. It is concluded that the efforts to lower the administrative hygienic levels of styrene have been in the right direction.

Acute effects of m-xylene inhalation on body sway, reaction times, and sleep in man.

Nine male volunteers were exposed to either a constant or a fluctuating exposure pattern of m-xylene with a time-weighted average exposure concentration of 200 ppm in both cases. The subjects remained sedentary throughout the exposure, or the exercised at 100 W for 10 min at the beginning of the morning and the afternoon sessions. In another experiment, 12 sedentary male volunteers were exposed to a fixed 200 ppm of m-xylene. The effects of m-xylene on body sway, reaction time performance, and overnight sleep were measured. Body balance was stabilized after exposure to the peaks of 400 ppm of m-xylene in both sedentary and exercising subjects. Simple visual reaction times were prolonged after the peak exposures at rest whereas auditive choice reaction times were prolonged after peaks combined with exercise. Exposure to m-xylene at a constant level of 200 ppm did not affect the ratio of "active" to "quiet" sleep in the volunteers as measured with the static charge sensitive bed recording, but decreased slightly the number of body movements in bed. On the next morning no changes were found in body sway and reaction time performance as compared to the morning before exposure.

Neurotoxicity in workers exposed to styrene.

Quantitative electroencephalography (EEG) for 99 workers exposed to styrene in the reinforced-plastics industry was analysed and compared with exposure parameters. The work places and factories from which the subjects were selected had been evaluated previously, and exposure levels were known relatively accurately. That information and data on individual exposures were combined to create an exposure index, which reliably reflected long-term exposure to styrene in various occupational settings. All of the subjects underwent careful medical and neurophysiological examinations. Quantitative EEG was recorded on 19 channels and analysed for absolute and relative power, asymmetry, coherence, frequency distribution, and statistical normative data base comparisons (neurometrics). When the workers were divided into three groups on the basis of exposure, workers with the highest exposure had significantly more EEGs classified as abnormal and had higher absolute EEG power in alpha band in the fronto-temporal regions of the brain. The findings indicate that abnormalities can occur in cerebral function even after relatively low mean exposures. We conclude that the efforts to lower regulatory hygienic levels of styrene are justified.

Metabolic control and progression of complications in insulin-dependent diabetic patients after kidney transplantation.

Patient survival and progression of complications were monitored for 3 years after kidney transplantation in 29 type-1 diabetic patients. Ten age-matched, non-diabetic kidney-transplanted patients served as controls. Five diabetic patients died during follow-up (three cardiovascular events, two infections), three diabetic patients had a non-fatal myocardial infarction and four developed cerebrovascular complications after transplantation. Of the diabetic patients, 69% suffered from proliferative retinopathy before transplantation; 20% of them improved, 65% remained unchanged and 15% deteriorated after transplantation. Motor but not sensory conduction velocity measured from the nervus medianus improved after transplantation. Autonomic neuropathy was observed in 50% of the patients and was unaffected by transplantation. Glycaemic control did not improve significantly during follow-up (HbA1, 10.6 +/- 0.5% before and 9.5 +/- 0.6% 3 years after transplantation). Body weight increased in both diabetic and non-diabetic patients within 3 years after transplantation (from 68 +/- 2 to 77 +/- 6 kg in diabetics, P less than 0.01; from 167 +/- 4 to 77 +/- 6 kg in non-diabetics, P less than 0.01). Subcutaneous fat thickness measured from computer tomography scans of the calf increased in diabetic patients from 5.0 +/- 0.6 to 6.1 +/- 0.9 mm (P less than 0.05). However, the cross-sectional areas of triceps and calf muscles did not increase, suggesting that the increase in body weight was solely due to an increase in fat. It is clear that diabetes-related complications continue to progress and are not influenced by a successful kidney transplant.

Sustained high plasma 5-aminolaevulinic acid concentration in a volunteer: no porphyric symptoms.

The pathogenesis of the acute porphyric attack is not known. One hypothesis is that porphyrin precursors, especially 5-aminolaevulinic acid (ALA), are toxic for neuronal tissue. This was tested by infusing ALA in a male volunteer after a loading dose at a rate of 50-80 mg h-1 for 92.5 h. During the experiment plasma ALA concentration was 9-11 mumol 1-l and porphobilinogen concentration 3-6 mumol 1-l which are the levels seen during acute attacks. Urinary excretion of these porphyrin precursors was also markedly increased. ALA infusion caused no subjective symptoms and no change in pulse rate, blood pressure, or autonomic nerve function or conduction velocity of peripheral nerves. Photosensitivity was not demonstrable. It is concluded that sustained high plasma ALA concentration does not cause porphyria-like symptoms.

Vibration sensitivity thresholds: methodological considerations.

Vibration sensitivity thresholds were studied in 12 healthy volunteers using 25, 50, 100 and 250 s-1 stimulus frequencies from an instrument with automated and manual modes ('Vibra Mk II'). For the automated mode, a forced choice principle was adopted. All measurements were performed from both the knuckle of the IInd metacarpophalangeal joint and the medial malleolus on four successive days. In addition, a conventional tuning fork method for vibration sensitivity was applied. The results show high interindividual and intraindividual variation in all measurements. The threshold values measured by the automated system were significantly lower than those by manual system at all frequencies. The largest variation was seen at 250 s-1 and the most uniform values at 100 s-1. There was a clear difference between the values from knuckle and medial malleolus, the values in the foot being lower. There was no learning effect. Clear age-related increase in vibration thresholds was observed. Conventional tuning fork-method showed clear differences in vibration sensitivity between hand and foot, in accordance with computer assisted method. The higher sensitivity of the automated method compared to the manual makes this the method of choice, although further investigations to finish the method and to build up a broader reference material is desirable.

Posturography and the dizzy patient: a neurological study of 133 patients.

A total of 133 dizzy patients under the age of 60 years were examined using a stable balance plate (posturography, PG). All the patients were thoroughly examined neurologically before PG and classified into 7 diagnostic categories. Comparison was made between these categories and PG results. The referent group consisted of 116 healthy individuals. The patients with CNS lesions had more body sway than controls or the patients with peripheral vestibular lesions, whose sway did not significantly differ from that of the controls. The PG parameters that most clearly separated the patients from the controls were the total length of the movement of the center of gravity, and the sway in lateral and antero-posterior directions. Analysis of the frequency of the sway or calculation of the Romberg index did not reveal significant differences between the categories. Men swayed more than women. Age did not correlate with PG results. Stable posturography offers useful quantitative supplementary information as a part of the examination of a dizzy patient. Increased body sway suggests a lesion in the CNS.

Occupational exposure to solvents and cerebellar, brainstem and vestibular functions.

Forty-eight persons (age 44, SD 9 years) exposed to paint solvents and 40 nonexposed referents (age 45, SD 9 years) were examined. The duration of exposure was 4 to 30 (mean 20) years and the life-time exposure level was estimated to have been 10 to 330 (mean 60%) of the hygienic standard. The methods used were a neurological examination, electroencephalography, brainstem auditory-evoked potentials, electronystagmography, and posturography. Life-time exposure was estimated on the basis of a detailed occupational history and environmental measurements made at the work places over several years. The average weekly alcohol consumption was established in a detailed interview. Due to the small number of subjects examined, the study was inconclusive. The findings classified as abnormal were slightly more common in the exposed than in the referents, and in the persons who used alcohol than in the non-users. The differences were not statistically significant, and no exposure-response relationships were found.

Diagnostic value of electroencephalography and brainstem auditory evoked potentials in dizziness.

Electroencephalogram (EEG) and brainstem auditory evoked potentials (BAEP) were recorded from 142 dizzy patients. The results were compared with those obtained by other neurological examinations of the same patients. Thirty-three percent (N = 44) of the patients had an abnormal EEG: 21% (28) showed focal abnormality, 12% (16) irritative features, and 10% (13) generalized disturbance. There were no differences in the distribution of abnormal EEGs in different diagnostic categories of dizziness, but irritative findings were not found in the cases of peripheral vestibular or psychogenic disturbances. EEG findings in 3 patients suggested temporal epilepsy, correlating with the clinical picture. BAEPs were abnormal in 18% (N = 21) of the recordings. There were 3 cases of MS and 5 ischaemic lesions in the vertebro-basilar region. Twelve of the 13 other patients with abnormal BAEP showed evidence of CNS pathology with other methods. EEG abnormalities were mostly non-specific; however, the irritative findings suggested cerebral pathology, such as epilepsy. An abnormal BAEP offers reliable evidence for brainstem lesion and is thus a useful examination in dizziness.