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Frequencies and amplitudes of miniature endplate potentials (MEPP's) were recorded from neuromuscular junctions of the rat phrenic nerve-diaphragm preparation in vitro. Superfusion of the preparations with Ringer solution containing thallium acetate (Tlac) gradually increased the frequency of MEPP's by a factor of 10 within 30 min (1 X 10(-3) mol/l Tlac) and 180 min (5 X 10(-4) mol/l Tlac), whereas the amplitude of MEPP's remained unchanged. Frequency of MEPP's fitted a Poisson-distribution which persisted during superfusion with Tl+-Ringer. Sub-MEPP amplitudes remained unaffected by the action of thallium. It is concluded that thallium interferes presynaptically with spontaneous transmitter release.

A method is described for determining riboflavin excretion in urine by thin-Layer chromatography. The sample will be preliminarily purified on Permutit T with subsequent separation of riboflavin by thin-layer chromatography on Kieselgel HR with pyridine--acetic acid--water as an eluant. Substances interfering with the fluorescence of riboflavin can be eliminated through the procedure. Riboflavin remission is measured by a chromatogram-spectralphotometer with fluorescence equipment. Between 0.02 to 0.5 mug riboflavin intensity of fluorescence is proportional to the concentration of riboflavin.

In order to assess the degree of thallium exposure in a population living around a thallium emitting cement plant in a small city in North-West Germany thallium levels in 24 h urine samples of 1,265 subjects and in hair samples of 1,163 subjects were determined. Urinary thallium levels in two groups of subjects living in an urban and a rural area of West Germany were determined for reference. As compared to these subjects the population living around the cement plant exhibited obvious signs of increased thallium intake. The mean urinary thallium concentration was 2.6 micrograms/l and ranged up to 76.5 micrograms/l. In contrast, the mean urinary thallium levels of the two reference groups were 0.2 and 0.4 micrograms/l, respectively. Hair thallium levels of the population living around the cement plant were also markedly increased (mean: 9.5 ng/g). The major route of the population's increased intake of thallium was found to be the consumption of vegetables and fruit grown in private gardens in the vicinity of the cement plant. As was shown by chemical analyses vegetables and fruit grown in these gardens were contaminated by thallium-containing atmospheric dust fall-out caused by emissions of the cement plant. The pulmonary route of uptake as well as other sources did not seem to play a significant role in the population's exposure to thallium. Polyneuritic symptoms, sleep disorders, headache, fatigue and other signs of psychasthenia were found to be the major health effects associated with increased thallium levels in urine and hair. No positive correlation was found between the thallium levels in hair and urine and the prevalence of skin alterations, hair-loss and gastro-intestinal dysfunctions.

A number of air pollutants is known to affect the immune system resulting in alterations of the complement activity in serum. We determined the levels of C3c, one of the activation products of the component C3, in serum samples obtained from various population groups living in areas with different levels of air pollution in Northrhine-Westphalia (FRG). The results show that the serum C3c levels tend to be increased in subjects living in areas with elevated levels of air pollution. By applying a linear regression model it can be demonstrated that a significant part of the variance of the C3c concentrations is explained by the residence area factor after making allowance for the effect of various confounders. The increase of the serum C3c concentrations appears to result from an increased activation of the complement component C3. The underlying mechanisms as well as the pathophysiological significance of these findings are unknown.

Lead concentrations were measured in the deciduous teeth (incisors) of 302 children living in a lead-smelter area in the FRG (Stolberg, Rheinland) and of 86 children living in a nonpolluted rural area (Gummersbach, Bergisches Land). Blood lead levels were determined in 83 of the children living in the lead-smelter area. On average, tooth lead levels of children living in the smelter area (mean: 6.0 microgram/g; range: 1.49-38.5 microgram/g) were significantly higher than those of children living in the rural area (mean: 3.9 microgram/g; range: 1.6-9.4 microgram/g). Blood lead levels were 6.8-33.8 microgram/100 ml (mean: 14.3 microgram/100 ml). Children of lead-workers had on average higher tooth lead and blood lead levels than children of people who were not lead-workers. Tooth lead levels increased with increasing duration of residence in the lead-smelter area and with the degree of local environmental pollution by lead, as indicated by the lead content of the atmospheric dust fall-out around the children's homes. The correlation coefficient of tooth lead vs blood lead was 0.47. The intra-individual variability of tooth lead levels was low (r = 0.86), and tooth lead levels of brothers and sisters were similar (r = 0.75), suggesting that tooth lead may be used as a representative and reliable indicator of long-term lead exposure.

Between 1982 and 1986 several surveys were carried out to determine the levels of lead and cadmium in blood, urine, and shed deciduous teeth (incisors only) of children living in rural, suburban, urban, and industrial areas of North-West Germany. Blood lead (PbB) and blood cadmium (CdB) were measured in about 4000 children. In rural, suburban and urban areas the median PbB levels vary between 5.5 and 7 micrograms/dl, with 98th percentiles varying between 10 and 13 micrograms/dl. The median CdB levels are between 0.1 and 0.2 microgram/dl, with 95th percentiles between 0.3 and 0.4 microgram/l. Children from urban areas have significantly higher PbB levels than children from rural and suburban areas. Regarding CdB no differences could be detected. Children living in areas around lead and zinc smelters, particularly those living very close to the smelters, have substantially increased PbB and CdB levels. Children from lead worker families also have substantially increased PbB and CdB levels. The lead levels in shed milk teeth (PbT) were determined in about 3000 children. In rural, suburban and urban areas the median PbT levels are between 2 and 3 micrograms/g, with 95th percentiles between 4 and 7 micrograms/g. Children from urban areas have significantly higher PbT levels than children from rural and suburban areas. The highest PbT levels (on a group basis) are in children from nonferrous smelter areas. The median levels of lead in urine (PbU) are between 6 and 10 micrograms/g creatinine, with 95th percentiles between 20 and 30 micrograms/g creatinine. Children from polluted areas have higher PbU levels than children from less polluted areas. The median levels of cadmium in urine (CdU) are in the order of 0.1 microgram/g creatinine, with 95th percentiles being in the range of 0.5 and 1.0 microgram/g creatinine. Girls have higher CdU levels than boys. There are no differences between groups of children from different areas. Children from lead worker families have higher PbU and CdU levels than otherwise comparable children. The results of the present studies indicate a further decrease of PbB in children from North-West Germany since the CEC blood lead campaigns carried out in 1979 and 1981. The decrease of lead exposure also seems to be reflected by a decrease of tooth lead levels.

1. The influence of silybin-dihemisuccinate, a derivative of the flavonolignane silybin from silybum marianum L. Gaertn., on fatty acid biosynthesis of rat liver was studied measuring the radioactivity incorporation of [1-14C]-acetate and 3H2O in fatty acids of the postmitochondrial supernatant of liver homogenates and in fatty acids of liver slices as well as the activities of enzymes involved in do novo synthesis of fatty acids. 2. In the postmitochondrial supernatant of liver homogenates or in liver slices, prepared 30 or 60 min after i.v. injection of 150.6 mg/kg silybin-dihemisuccinate, radioactivity incorporation of 14C-acetate or 3H2O in fatty acids was lowered by about 25%. Adding silybin-dihemisuccinate to incubation mixture in vitro in the concentration of 0.45--0.6 mmol/l silybin the radioactivity incorporation was linearly diminished with increased concentration of silybin. 3. After in vitro addition of varying concentrations of silybin to incubation mixtures in the presence of 0.1 mmol/l silybin activities of acetyl-CoA-carboxylase, fatty-acid-synthetase and ATP-citrate-lyase were diminished by about 50%, while activity of NADP-malate-dehydrogenase was lowered by 20% in the presence of 1 mmol/l silybin. 4. Our results suggest that silybin caused an unspecific and, under in vivo conditions, transitory inhibition of fatty acid synthesis in rat liver.

Neurofibromatosis (also known as multiple neuroma and Recklinghausen's disease) is caused by a deficient proliferation of the neuroectodermal and mesodermal crest. Therefore, a wide variety of symptoms can be found including cutaneous, neurological, ophthalmological, visceral and osseous changes. Hallmark of this disease are so-called café-au-lait areas of pigmentation, or spots. The ENT specialist is confronted with bilateral acoustic tumours, peripheral nerve tumours, cutaneous tumours, tumours of the larynx and alterations of the facial bones. Eight cases of neurofibromatosis are demonstrated, and recent literature is discussed. Management of patients suffering from neurofibromatosis is mainly palliative and symptomatic. To achieve a good result in treatment there must be an effective cooperation between specialists of different disciplines.

Results from neuropsychological tests, collected under double-blind-precautions, were evaluated for 115 schoolage children (mean age: 9.4 years) living in a lead smelter area (Stolberg, FRG). Tooth-lead concentrations (PbT) from shed incisor teeth as measures of longtime lead-exposure were available for these children (mean = 6.16 ppm; range: 1.9-38.5 ppm), and for 83 of them blood-lead concentrations (PbB) were available as well (mean = 14.3 micrograms/dl; range: 6.8-33.8 micrograms/dl). The following functional capacities were tested: intelligence (German WISC), perceptual-motor integration (Göttinger Formreproduktionstest = GFT, Diagnosticum for Cerebralschädigung = DCS), reaction performance (Wiener Determinationsgerät), finger-wrist tapping-speed, and repetitive cancellation-performance (Differentieller Leistungstest). In addition standardized behavior ratings were obtained by the examiners, the mothers, and the teachers. Multiple stepwise regression-analysis (forced solution) was calculated for outcome-variables and Pb-tooth, including age, sex, duration of labor, and socio-hereditary background as covariates. Significant (P less than 0.05) or near-significant (P less than 0.1) association was established between Pb-tooth and GFT-performance (errors), reaction-performance (false reactions), and four behavioral dimensions as rated by the mothers, namely distractability, restlessness, lack of information, and wasting of time; the proportion of explained variance never exceeded 6%, however. No significant association was found between PbT and WISC verbal-IQ after the effects of "socio-hereditary background" had been eliminated, although there was still a tendency for high level-children (PbT greater than 10 ppm) to be inferior to low level-children (PbT less than or equal to 4 ppm) by 4.6 IQ-points after correction for confounding. There was a near-significant, inverse relationship between finger-wrist tapping-speed and Pb-blood. The results are discussed within the framework of attention-deficit disorder, and compared to neurobehavioral Pb-effects from animal-experiments, which provide suggestive evidence for a causal relationship between developmental lead-exposure and certain neurobehavioral deficits.

Evidence is presented showing that serial choice reaction performance is disrupted at low blood lead levels (PbB), and that parametric variation of task characteristics modulates the degree of disruption. This evidence is based on two independent studies in 6- to 9-year-old children living in two lead smelter areas in the cities of Nordenham (N = 114) and Stolberg (N = 109) in West Germany. Average PbB was 8.2 micrograms/100 ml (4.4-23.8 micrograms/100 ml) in the Nordenham sample and 7.4 micrograms/100 ml (4.2-18.0 micrograms/100 ml) in the Stolberg sample. Serial choice reaction performance was assessed by means of the Vienna reaction device in which a random sequence of light and tone signals has to be answered by pressing appropriate response buttons. Correct (hits) and false responses (errors) were evaluated as performance measures, and signal rate was varied in order to achieve easy and difficult task conditions. Exposure-related performance deficit was more pronounced for errors than for hits, more clearcut for high than for low signal rates, and proved significant in both studies after correction for confounding using confounder models of different complexities. Some features of the observed deficit resemble clinical observations in children presenting with attention deficit disorder.

Twelve different groups of fine mine dusts were examined for their in vivo aggressivity by intraperitoneal injection. Twelve months after injection of the dust, quantitative morphometric analysis of the lymph nodes was carried out to determine (a) the extent of the typical quartz reaction, (b) the in vivo cytotoxicity, (c) the size of the lymph nodes. Different fine dusts showed significant variations in parameter (a) and (c). In the second part of the investigation, the results of the lymph node tests and of in vitro cytotoxicity tests, and also the quartz contents of the dusts were fed into a data matrix and subjected to correlation analysis and principal component analysis. The following hypotheses were arrived at to explain the effect of the fine dust in vivo: (1) The amount of fine dust which penetrates into the lymph nodes is dependent on its in vitro cytotoxicity (Factor A). This is not related to the quartz content of the dust and is not inhibited by PVNO. (2) The specific fibrogenic activity of the fine dust within the lymph node is primarily dependent on its quartz content (Factor B). It appears that this effect is inhibited by PVNO. (3) The total fibrogenic activity depends on a combination of Factor A and B.

Sera of 122 persons were examined by the neutralization and latex-agglutination inhibition tests for antibodies against Polio type I, Coxsackie virus type A 9 and B 4, as well as Echo virus type 9. With increasing age there was a titre difference between latex-agglutination inhibiting and neutralizing antibodies, due to the earlier fall in the former. These antibodies, contrary to neutralizing ones, were in the lower titre region. The results confirmed the usefulness of the latex-agglutination inhibition test in the diagnosis of acute enterovirus infections.

Measurements of carboxyhemoglobin (COHb)-content from about 13,000 inhabitants of various sites in western North Rhine-Westphalia are presented. Analyses were part of surveys on the effects of air pollution conducted between 1975 and 1980 in five designated, polluted areas. Determinations were executed in the Medical Institute for Environmental Hygiene, Duesseldorf, on behalf of the Ministry of Labour, Health and Social Administration. Analysis of blood samples for CO-content was performed by gas chromatography. Carboxyhemoglobin levels were calculated by reference to the individual hemoglobin levels. Our surveys have been conducted during several years and included different seasons. Before 1977, fifty years old men were investigated. Until 1978, sixty years old men were studied. In 1979 and 1980, sixty years old women and ten years old children were additionally incorporated into the survey. Statistical analysis of data included variables which influence personal CO-burden such as smoking, and in the case of non-smokers indoor air exposure through passive smoking, use of gas facilities and heating in the flat, as well as occupational exposure. Besides, the influence of age, sex and location was considered. The average COHb-level of the populations under study was expressed as the median of the distribution. The distribution-free Mann-Whitney U-test served for assessment of differences between groups. As a further parameter, the percentage of the measurements greater than 2,5% COHb was chosen, because it was thought to be more relevant to risk populations, i.e. people suffering from Angina pectoris. As expected, tobacco smoking exerted the greatest influence on COHb-level. In non-smokers a trend, indicating a relationship between indoor air pollution and COHb-content could be observed. If high CO gas such as coke gas was used in flats with gas facilities COHb-levels were significantly raised. Surveys performed in 1979 and in 1980 showed a sex-dependent difference between median COHb saturations, women having lower values than men. The difference of these figures between adults and children is statistically significant. Comparisons between adult nonsmokers from various sites prompted a significant difference only in the case of the Oberbergischer Kreis (County), having the lowest median COHb-value. The highest COHb-levels by far were encountered in the city of Duisburg in January 1979, when very unfavourable meterological conditions (Smog alarm, degree 1) were present. The median COHb saturations reached on this occasion were very near to the limits considered to be critical for populations at special risk.

To test the influence of hypoxia upon the pulmonary gaseous exchange and the hemodynamics of the pulmonary circulation 12 healthy test-persons at the age from 33 to 47 years (mean = 36.7 years) were submitted to a pulmonary and cardiocirculatory basis-investigation with determination of VK, VE, VO2, VCO2, Hb, PO2A/a, PCO2A/a, pH, BE, HR, ECG, PVd, PAp, SV, HZV, RL. These investigations were followed by stress examination by means of the bicycle-ergometry in four rectangular steps under conditions of normoxia from 95.5 to 97.3 kPa, x = 96.5 kPa (716 to 730 torr, mean = 723.6 torr) and of hypobarohypoxia in a low-pressure chambre at 66.5 kPa (500 torr) each of 6 min duration. Under the influence of hypoxia a PO2a-decrease in the sense of partial insufficiency could be already observed at rest under conditions of a decreased alveolar oxygen-partial-pressure. At this simultaneously increases the CO2-exhalation. At the same time was found a significant increase of the systolic peripheric and the diastolic pulmonary-arterial pressure. At the increasing step-by-step ergometric employment under conditions of the hypoxia stress were growing significance evidence of different reactions of the pulmonary and cardiocirculatory parameters occurred.

This experiment was designed to study the degree of recovery from lead-induced neuro-behavioral deficit after normalization of blood lead-level (PbB). Female Wistar-rats were given a diet containing lead-acetate (2260 ppm Pb) for 60 d until mating, giving rise to a PbB-increase from 53 microgram/d1 (before mating) to 84 microgram/d1 (after weaning). Lead-exposure of their male offspring was continued for 4 months with their PbB levelling off at 40 microgram/d1 (table 1). Lead-feeding was discontinued thereafter for another 4 months, PbB declining to a final level of 12 microgram/d1 (table 1). These animals were then compared for neurobehavioral functions to age-matched controls with respect to discrimination-learning (Lashley jumping-stand) and motor activity (open field-test). In addition recovery from initial loss of body-weight after partial food-deprivation was measured, known to be retarded at elevated PbB. The results may be summarized as follows: Formerly Pb-treated animals subsequently raised on a lead-free diet resulting in PbB-normalization within 4 months as compared to untreated controls exhibit (1) significant retardation of recovery from initial loss of body-weight (fig 4), (2) significant increase of error-repetitions in discrimination-learning (table 4; fig. 5) indicating disturbances of learning-performance without a change in learning-speed, and (3) significant hypoactivity (ambulation) without a significant change of other variables of open field-behavior (table 5; fig. 6). These results demonstrate, that some neurobehavioral and systemic symptoms of Pb-related dysfunction persist even after normalization of PbB, thus indicating partial irreversibility of Pb-induced damage.

We investigated the effects of cadmium and lead on the oxidative metabolism of mouse peritoneal macrophages induced either by phagocytosis of zymosan particles or by membrane perturbation with phorbol myristate acetate (PMA) without phagocytosis. Oxidative metabolism activity was measured by chemiluminescence in the presence of lucigenin. Furthermore, cell viability was tested by dye exclusion test and phagocytic activity was measured by ingestion of latex particles. Within the first hour of exposure to the metals the effects of cadmium and lead in peritoneal macrophages were the same. The oxidative metabolism induced by PMA was enhanced by both metals, the zymosan-induced oxidative metabolism was reduced, markedly by cadmium and weakly by lead. Cell viability was not affected. After 20 h of exposure the effects of cadmium and lead were different. Cadmium did not alter either the oxidative metabolism induced by zymosan and PMA or phagocytosis of latex-particles. Lead concentration-dependently suppressed the oxidative metabolism induced by zymosan and PMA as well as phagocytosis of latex-particles. However, cadmium reduced cell viability concentration-dependently in contrast to lead that reduced cell viability only slightly.