Computed tomography and psychometric test performances in patients with solvent induced chronic toxic encephalopathy and healthy controls.

Patients with chronic toxic encephalopathy caused by occupational exposure to organic solvents and diagnosed between 1976 and 1981 have been re-examined during a follow up period of 21-88 months (median 48). Thirty two patients underwent computed brain tomography (CT), were retested psychometrically, and the results were compared with a group of age matched control subjects from the same socioeconomic level. The age of the patients was 33-69 (median 55) and they had been exposed to organic solvents for 7-50 years (median 26). The CT examinations were quantified by linear measurements on the films of the four largest sulci, the minimum width of the cella media and the third ventricle. Bifrontal horn, bicaudate, and third ventricle--Sylvian fissure distances were also measured; and measurements were adjusted for variation in skull diameter. No differences were found between the patients and controls. Most of the measures were correlated with age, to a somewhat higher degree in the patients. The patient-control differences did not increase with increasing age of the subjects. Psychometrically the patients performed worse than the controls despite adjustments for possible differences of intellectual level in the two groups. In the patients correlations were found between some of the CT measures and psychometric test performances suggesting slower psychomotor speed and attention difficulties among subjects with central and cortical brain substance reduction. No such correlation was found in the control group. It is concluded that patients with solvent induced chronic toxic encephalopathy have no severe loss of brain substance.

Acute and long-term airway hyperreactivity in aluminium-salt exposed workers with nocturnal asthma.

Nineteen young male workers exposed occupationally from 1975-1977 to inhaled particles of aluminium fluoride or sulphate at 2 plants, developed nocturnal wheezing and breathlessness with reversible airways obstruction after an average of 4 months employment. At standardized methacholine provocation tests (MPT), 17 of 19 workers with normal spirometry showed airway hyperreactivity with a fall of FEV1 of greater than or equal to 15% after 0.1% methacholine. We followed 15 initially asthmatic workers for 2-5 years with MPT. Mean TD 15% FEV1 in 11 workers did not change significantly after an average of 41 months of non-exposure. Six workers continuously exposed for 48 months also failed to change their TD 15% FEV1 MCh. In 1983, only one subject had returned to normal airway reactivity. We have no reason to suspect inducing agents other than aluminium salts.

Effects of long-term exposure to solvents in the paint industry. A cross-sectional epidemiologic study with clinical and laboratory methods.

The effects of organic solvents on 50 male workers exposed 5-46 (mean 18) years were studied with a cross-sectional design. Referents were matched pairwise according to age and education. An analysis of confounders confirmed good comparability between the two groups. As indicators of organic brain dysfunction regional cerebral blood flow was measured and the power spectrum of the subjects' electroencephalograms was analyzed, the former being reduced 4% and the latter showing increased power in the delta and beta bands in the exposed group. Symptoms of brain dysfunction were significantly more frequent among the exposed subjects and showed an exposure-effect relationship. Neuropsychological tests revealed definite indication of brain dysfunction in 14% of the exposed subjects in comparison to none in the reference group. The exposed subjects performed significantly worse than the referents in tests measuring focused attention abilities. A neurophysiological examination of the peripheral nervous system showed no difference between the groups. Clinical chemistry demonstrated no differences that could be explained by solvent exposure.

Lead in finger-bone analysed in vivo in active and retired lead workers.

In 75 active lead workers the median lead level in finger-bone (bone-Pb), as determined in vivo by an X-ray fluorescence method, was 43 micrograms/g (range less than 20-122). In 32 retired workers the median level was even higher, 59 micrograms/g (range less than 20-135), which indicates a slow turnover rate of lead in finger-bone. This was confirmed in 18 of the "active" workers, in whom bone-Pb was studied in connection with an exposure-free period. In spite of a significant decrease in blood-lead levels (B-Pb), no systematic change of bone-Pb occurred. There was an increase of bone-Pb with time of employment, but with a large interindividual variation. No association was found between bone-Pb and present B-Pb in the active lead workers. However, in the retired ones, B-Pb rose with increasing bone-Pb. The bone-lead pool thus causes an "internal" lead exposure.

Regional cerebral blood flow and verbal memory after chronic exposure to organic solvents.

Regional cerebral blood flow (rCBF; 133Xe-inhalation method) was investigated in 32 industrial workers (age: 51 +/- 9 years) who had been exposed to organic solvents during an average of 24.5 years. The measurements were made at rest and during learning of associated word pairs. The resting flow level was 17% lower than expected for normal subjects of similar age and the activation-induced changes of rCBF during the test lacked the frontal activation normally seen. Significant correlations between age, length of exposure, and rCBF level were found. In order to control for the age factor, results were also calculated from two subgroups of similar age but with very different levels of exposure (13 and 31 years of average exposure). The two groups differed only slightly in resting rCBF. A marked difference was, however, seen during activation, with significant post-central flow increases recorded in the lower-exposed group only. The results indicate the potential of the rCBF method for elucidating functional cortical changes related to neurotoxic effects of organic solvents.

Why is the patient with lead intoxication not light sensitive?

Ever since the 1930s, when it was found that the concentration of protoporphyrin (PP) in the red blood cells is markedly increased in lead workers, it has been keenly debated why these persons, like patients with certain types of porphyria, are not hypersensitive to light. The answer came in the 1970s when it was realised that erythrocyte-PP in lead poisoning is not free, as it is in porphyria, but is bound to zinc (ZPP). Free PP can pass through the erythrocyte membrane into the tissues, while ZPP remains confined in the red blood cells. On exposure of PP in the skin to sun shine, the molecule is stimulated to release energy, which causes blisters, reddening, swelling and other symptoms of hypersensitivity to light.

beta-Carotene in the treatment of erythropoietic protoporphyria. A short review.

A review of published trials with beta-carotene and/or canthaxanthin treatment of erythropoietic protoporphyria is presented. Increased tolerance to sunlight is reported in about 85% of the cases in uncontrolled studies. In the only controlled trial on record no difference was found between beta-carotene and placebo. Correlations between the results of carotenoid treatment and phototests have been reported in some studies, but denied in others. During treatment the protoporphyrin levels in erythrocytes were significantly increased in one study, but decreased or unaffected in others. A possible mechanism of photoprotection by beta-carotene is briefly presented. To date no serious side effects or hypervitaminosis-A induced by beta-carotene have been reported.

Antagonistic effects of zinc and aluminum on lead inhibition of delta-aminolevulinic acid dehydratase.

In vitro and in vivo studies regarding the influence of metals on delta-aminolevulinic acid dehydratase activity in erythrocytes indicate that a lead concentration of 4 micrometer/l completely inhibits the enzyme. Zinc activates the enzyme both in vitro and in vivo at concentrations greater than 76 micrometer/l. Aluminum has an inhibitory effect at all concentrations in vitro whereas it activates the enzyme in vivo. Zinc and aluminum together activate the enzyme in vivo. The in vitro activation of zinc is inhibited by increasing concentrations of aluminum. Aluminum and lead together depress the enzyme activity in an additive way that can be reactivated by the addition of zinc.

Oral carotenoids for photohypersensitivity in patients with erythrohepatic protoporphyria, polymorphous light eruptions and lupus erythematodes discoides.

beta-Carotene and canthaxanthin in a dose of 75--250 mg a day by mouth reduced the symptons of exposure to the sun in all 7 treated patients with erythrohepatic protoporphyria (EPP), in 15 of 18 with polymorphous light eruptions (PMLE) and in 3 of 4 with lupus erythematodes discoides. In the EPP group the protoporphyrin level tended to vary inversely with that of the serum carotenoids. The level of retinol-binding protein in plasma remained unchanged despite a substantial rise in the concentration of the serum carotenoids. Estimation of the minimal erythema dose for unfiltered light from a Xenon lamp in 7 patients with PMLE showed an increase in only 1 patient. Neither clinical examination nor repeated laboratory studies revealed any serious side effects of the treatment.

Effect of age and diet on delta-aminolevulinic acid dehydratase in red blood cells.

ALA-D activity measured in the red blood cells of different species show considerable variations. Among the adult animals, rabbits have the highest activity and dogs, the lowest. It is a zinc-dependent enzyme and its activity is related to the age of the animals as well as the availability of zinc in the diet during the early growth period. Rats at partus have the highest ALA-D activity ever registered in any animal species and it decreases drastically during the early growth period. The red blood cells of newborn human babies have 50% higher ALA-D activity than that of adult man. When rats during their early growth period are fed on a diet containing 0.08 mmol zinc, there was a reduction in the enzyme activity whereas adult rats fed on diets containing higher and lower amounts of zinc did not show any change.

Neurophysiological observations after chronic styrene exposure.

Thirty-three styrene exposed workers from three different industrial sites were examined with electroencephalography and motor and sensory neurography. The three groups had respective styrene exposures of clearly above the threshold limit value (50 ppm), at about this level, and clearly below it. The neurophysiological results were compared with those of a group of normal controls and a group of 17 patients judged to suffer from sequelae after long-term heavy exposure to organic solvents (mainly painters). Ten subjects in the styrene group presented signs of a mild sensory neuropathy with polyphasic sensory responses of a low amplitude. The same pattern was commonly found among the reference group heavily exposed to solvents. The ten subjects in the styrene group with mild polyneuropathy had a significantly higher age and significantly heavier styrene exposure than the rest of the group. Age difference could not explain the difference in the neurophysiological parameters, and therefore the contributing role of styrene exposure has to be considered. The electroencephalographic analysis showed no changes of the dominant alpha frequency. An increased amount of diffuse slow activity was seen in many of the heavily exposed mixed-solvent cases and was seen in some of the styrene-exposed cases without a clear relation to degree of exposure. An increased occurrence of fast activity in central and precentral areas of the brain was found in the styrene group, as well as in the mixed-solvent group. This pilot study indicates that the same type of neurophysiological changes from the strictly normal are seen among workers exposed to styrene as those found among a group of patients judged to suffer from sequelae after chronic exposure to various organic solvents. The neurophysiological "profile" is (a) sensory nerve responses with low amplitude and long duration, (b) somewhat low sensory conduction velocities, (c) close to normal motor neurographic findings, and (d) an increased amount of fast activity in central and precentral regions in the electroencephalogram in combination with normal occipital alpha activity.

Staphylococcus aureus in the throat: A saprophyte or a pathogen?

144 industrial workers were investigated for the presence of Staphylococcus aureus in the upper respiratory tract because 53 of them had complained of chronic throat discomfort. Significantly more patients with subjective throat complaints harboured Staph. aureus in the nose (49.1%) and throat (32.1%) than patients without such symptoms (27.4% and 9.9%, respectively). No Staph. aureus were found in throat swab cultures from 21 randomly selected individuals working in a similar factory where no chronic throat discomfort was reported and only 2 throat carriers of Staph. aureus were found among 66 medical undergraduates investigated. The staphylocci belonged to several different phage type patterns and could not be recovered on sedimentation plates or from machines or products. In the light of these and other findings it was suggested that the staphylocci accentuated an already existing damage of the mucous membrane of the throat, but seemed not to be the primary cause of the discomfort.

Antagonistic effect in vivo of zinc on inhibition of delta-aminolevulinic acid dehydratase by lead.

Delta-aminolevulinic acid dehydratase (ALAD) is an enzyme involved in the biosynthesis of heme, in which it catalyzes the condensation of two molecules of delta-aminolevulinic acid to one molecule of porphobilinogen. It is a sulfhydryl enzyme, which means, among other things, that its activity is inhibited by many heavy metals. In the present investigation rabbits were given either zinc or lead or both. Zinc had a strong activating effect on ALAD in vivo, and the inhibitory effect of lead was almost completely eliminated. A close positive correlation was found between ALAD in the red blood cells and zinc in the plasma, but there was no correlation between ALAD and zinc in the red blood cells. These observations are of particular interest in the light of recent findings, suggesting that zinc is an essential metal for ALAD.

Effect of ethanol and zinc on ALA-dehydratase activity in red blood cells.

Subcutaneous injection of zinc as sulphate to rats activates sigma-aminolaevulinic acid dehydratase (ALA-D) in red blood cells within few days of injection. This activation counteracts the inhibitory effect of orally administered ethanol.