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Die Malaria nimmt mit etwa 1000 jahrlich nach Deutschland importierten Fallen einen wesentlichen Stellenwert in der reisemedizinischen Beratung ein, insbesondere da es sich in ca. 80% der Falle um die gefahrliche Malaria tropica handelt, die ohne oder bei zu spater Behandlung beim Nichtimmunen todlich verlaufen kann. Die Malaria tropica wird meist bei Reisen in das tropische Afrika erworben. Die Schwierigkeiten bei der Beratung zur Malariaprophylaxe liegen in der zunehmenden Resistenzentwicklung der Plasmodien gegenuber den Malariamitteln, so das neben der Chemoprophylaxe auch die notfallmasige Selbstbehandlung vor der Reise besprochen und durch adaquate Medikamente abgedeckt werden mus. Es gilt insbesondere, die Malaria tropica zu verhindern bzw. rechtzeitig zu behandeln, notfalls durch den Reisenden selbst, wenn Malariaverdacht besteht und ein Arzt nicht kurzfristig erreichbar ist. Dies setzt aber voraus, das der Reisende weis, wann Malariaverdacht besteht. Jedes unklare Fieber in den Tropen und auch noch lange Zeit danach ist solange malariaverdachtig, bis das Gegenteil erwiesen ist.

An ion cyclotron range of frequencies (ICRF) heating experiment was performed on the Compact Helical System (CHS) device in order to identify the problems in establishing this as a reliable heating method. Radiofrequency heating was applied to plasmas with two ion species produced by ECH. Stored energy increased upto 2.2 kJ with the application of a 590 kW ICRF heating pulse, giving a heating efficiency comparable to that of NBI heating. More importantly, the `flat-top' of the stored energy was maintained during the pulse. Good heating was realized with 30% proton and 70% deuteron plasmas at high density (4*1019 m-3). It was found that the best discharges are dominated by electron ICRF heating, which seems to be the reason for the successful results. On the contrary, a flat-top in stored energy has never been obtained in discharges where ion heating dominates. The loss of high energy ions with large pitch angles produced by ion heating appears to degrade the performance and limit the duration of the heating. A similar degradation was encountered in previous ICRF heating experiments in helical systems. A newly designed detector was used to study the loss of the helically trapped particles

Aluminium (Al) exposure can result in Al accumulation in the liver and this metal can be toxic to the hepatic tissue at high concentrations. In the present study the model of the isolated perfused rat liver was used to investigate the hepatic handling of Al. Livers from male Wistar rats were perfused in a recirculating system for 240 min. The liver function remained unchanged at perfusate concentrations of Al ranging from 4.9 to 1530.0 micrograms/l. At higher Al levels of 6535.3-16694.9 micrograms/l signs of toxicity towards isolated perfused livers were observed as indicated by an increased release of the enzymes AST and ALT into the perfusate, a pronounced reduction of bile flow rate and a 50% suppression of oxygen consumption. The hepatic Al clearance was low and decreased with increasing concentrations of Al in the perfusate from 4.3 +/- 0.6 microliters/min per g liver at a nominal Al concentration of 9.1 micrograms/l in control perfusate to 0.04 +/- 0.02 microliter/min per g liver at the highest concentration group. There was almost a linear dose dependent retention of Al in the liver with 4.9-635.7 micrograms Al/l perfusate while at higher concentrations Al levels in this organ increased disproportionally. It is concluded that by using the isolated perfused rat changes of liver functions occur only at very high Al concentrations in the perfusate and that only negligible amounts of Al are eliminated by the liver.

An analytical method for the simultaneous determination of the pyrethroid metabolites cis and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, cis 3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid, 3-phenoxybenzoic acid and 4-fluoro-3-phenoxybenzoic acid in human urine samples is described. The urine is subjected to acid-induced hydrolysis followed by exhaustive solvent extraction, covering both conjugated and free acids, followed by a common derivatisation step yielding the corresponding methyl esters. Quantitation was by diastereomeric, capillary gas chromatography-mass spectrometry. It appears that 4-fluoro-3-phenoxybenzoic acid is a characteristic urinary marker for cyfluthrin exposure. The limits of determination are 0.5–1.0 μg L−1 urine depending on the metabolites concerned. The applicability of the method was tested on urine samples from pest control operators exposed occupationally to cypermethrin and cyfluthrin.

Bronchoalveolar lavage (BAL) has gained widespread use as a tool for investigating human lung diseases. In certain cases, it can be useful to obtain BAL material in a serial manner. There is convincing evidence from experimental and clinical studies that BAL can cause influx of neutrophils into the bronchoalveolar space. However, conflicting data have been reported on whether this side effect of BAL also affects previously nonlavaged lung areas. In addition, there is little information available on whether multiple repetitive BAL procedures cause damage to lung tissue. To reexamine the short-term effects of serial BAL procedures, the left lung of 10 cynomolgus monkeys was lavaged with five 20-ml aliquots of saline four times at 24-h intervals (Group A). 72 h after the initial BAL, the right lung was lavaged as a control. The percentage of neutrophils increased significantly (p0.05), with the greatest effect seen at 48 h (30.7 +/- 5.8 versus 0.8 +/- 0.3%, mean +/- SEM). No significant changes were observed in the control BAL of the right lung at 72 h. A multidisciplinary approach was used to assess the long-term effects of multiple BAL procedures. BAL was performed 14 times over 26 mo at 2-mo intervals (Group B, n = 5). The right lung was lavaged as a control 25 mo after the initial BAL. In addition to standard cellular BAL parameters, the concentrations of fibronectin, procollagen III amino-terminal peptide-related antigen, total phospholipids, and lactate dehydrogenase activity were measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Based on numerous publications dealing with the effects of microbial emissions on workers in waste processing plants and on few papers concerning the assessment of the environmental health relevance of microbial aerosols on people living in the vicinity of composting facilities, the current state of the art in this field is presented. With regard to occupational exposure the possible health effects like infections, toxicity and allergies are specified. Since to date only few studies have been made of populations exposed to microbial aerosols in ambient air, the environmental health aspects are reviewed in the context of a study of three compost plants in Hesse, where ambient air measurements as well as epidemiological investigations were carried out. Final recommendations are given and the research needs regarding the environmental health significance of microbial aerosols are formulated.

In this study the production of enterotoxin A-D and toxic shock syndrome toxin-1 (TSST-1) of 181 methicillin resistant (MRSA) and 100 methicillin sensitive (MSSA) Staphylococcus aureus first isolates from different patients was investigated. All the MRSA- and MSSA isolates in the study were collected in a period between 1993 and 1995 from specimens sent from 11 different acute care hospitals in the greater Düsseldorf area. As far as possible the isolates were matched according to ward and hospital. The isolates were collected in the same time period and matched for specimen from which isolated. Furthermore, only first isolates were analysed in both groups. No significant difference in the production of toxin of any type between MRSA and MSSA could be detected (51 and 40% respectively). When the individual toxins were analysed, again no significant difference between MRSA and MSSA was demonstrable (enterotoxin production by MRSA 40% and MSSA 36%, and TSST-1 16% and 8% respectively). Despite this, a slight tendency for MRSA to produce enterotoxin A and B and for MSSA to produce enterotoxin C was observed. In addition, generation of TSST-1 by both groups was independent of enterotoxin A-D production. Interestingly, no increase in the proportion of TSST-1- or enterotoxin-producing MRSA and MSSA isolates was observed in strains isolated from blood cultures from patients with a clinical diagnosis of sepsis. Genotypical pulsed-field-gel-electrophoresis (PFGE) and phenotypical (bacteriophage typing, lysotyping) characterization of the 181 MRSA isolates resulted in 28 different PFGE patterns (of which 19 were toxin producers) and 22 lysotyping groups (18 of which produced toxin). In summary, the investigated clinical S. aureus isolates showed no difference in their ability to produce toxin and this was independent of their sensitivity to methicillin.

Over a period of three years the incidence of methicillin resistant Staphylococcus aureus (MRSA) isolates in 11 hospitals in the greater Düsseldorf area was observed. From a total of 7,814 S. aureus isolates, 489 (6.3%) were methicillin resistant. From 198 different patients, MRSA first isolates and 291 second isolates could be cultured. Methicillin resistance among all S. aureus isolates from 11 hospitals in the greater Düsseldorf area, ranged from 0.5 to 7.8% dependant on the size of the hospital. The highest incidence (7.8%) was found in a 1,500 bed hospital and the lowest incidence in a smaller 200 bed hospital (0.5%). With respect to the distribution among clinical departments the highest incidence of MRSA isolates was found on intensive care units and surgical wards, 25.5% and 13.0% respectively. The commonest specimen from which the MRSA isolates were cultured were respiratory secretions (17.6%) followed by central venous catheter tips (12.8%). In terms of the drug resistance pattern: all isolates were resistant to the aminoglycosides and gyrase inhibitors, whereas between 80% and 90% were sensitive to fusidic acid, chloramphenicol and pyrimethamine-sulfamethoxazole. All the strains were sensitive to the glycopeptide antibiotics, vancomycin and teicoplanin. Strain typing of 181 available first isolates (from a total of 198 first isolates) by PFGE and phage lysotyping produced identical results in more than 90% of all cases. Twenty-eight different MRSA strain types were identified by PFGE and in total 23 lysotypes could be determined. During the period of investigation an increased incidence of MRSA on an intensive care unit was observed, in which a total of 204 MRSA (42% of the total number) were isolated. The strain typing using both methods showed that on that ICU eight different MRSA types were involved in this outbreak. A hygiene plan was implemented on the unit with considerable success in reducing the incidence and spread of MRSA.

Within the scope of the present study n = 183 MRSA isolates from the extended area of Düsseldorf and n = 93 international MRSA strains from seven different countries were typed by pulsed-field gel electrophoresis and two PCR methods (RAPD and 16S-23S-spacer amplification). The isolates could be subdivided into 30 different types by PFGE, into 21 by means of RAPD and 18 by 16S-23S-spacer amplification. PFGE had the highest discriminatory potential, however, a combined use of the three typing methods allows a more detailed differentiation even of those isolates with identical PFGE pattern. Both amplification procedures were rapid, easy in handling with reproductable results. For a temporary epidemiological analysis within 24 hours, both amplification methods could be combined. In case the investigated isolates were still suspected of showing a "clonal identity", they should be analysed by additional PFGE (lasting about four days). Although the international isolates were chosen by random selection, several MRSA strains with identical pattern could be found in different countries of the world. Some RAPD-, spacer- and PFGE pattern were constant over many years. This reflects a high genetic stability of single strains.

Pneumoconiosis is a disease caused by chronic exposure to mineral dust such as coal mine dust, silica and asbestos. Current concepts in the pathogenesis of pneumoconiosis suggest that the alveolar macrophage plays a central role in the outcome of this disease. Upon stimulation with mineral dust the macrophages secrete a number of fibrogenic cytokines among them tumor necrosis factor a (TNFa) which is considered to play a key role in mineral dust induced pneumoconiosis (Dubois etal., 1989; Donaldson, 1992; Donaldson etal., 1992; Vanhee etal., 1995). Recently, naturally occurring inhibitors of TNFa activity have been identified showing high affinity binding to TNFa (Brockhaus et al., 1990). These inhibitors have been characterised as extracellular domains of the TNFa receptors types I and II, respectively. In response to inflammatory stimuli that cause enhanced TNFa levels, they are shed from the cell surface and appear as extracellular receptors in body fluids (Porteu and Nathan, 1990). Since such extracellular soluble receptors are suggested to intervene in the regulatory mechanism for modulation of excessive TNFa activity (van Zee et al., 1992; Spinas et al., 1992), enhanced serum TNF-receptor levels may reflect overexpression of TNFa in response to chronic exposure of mineral dust. In order to study the role of soluble TNF receptor as an individual factor in pneumoconiosis development we investigated serum levels of sTNFRII in groups exposed to silica containing dust or asbestos with normal chest radiographics and in groups of patients with silicosis and asbestosis.

Hair analysis comprises the determination of minerals, trace elements and drugs. It is applied in Germany with increasing frequency in the recently established field of environmental medicine for biological monitoring of the internal metal/metalloid exposure. Besides a number of advantages hair analysis is impaired by the difficulty-to distinguish between endogenous and exogenous sources of metals in hair. Except for methylmercury, there are no critical limit values for trace elements in hair available. However, valid reference values for some metals and for nicotine in hair have been recently presented in the German Environmental Survey. The significance of selected substances in hair are as follows: Aluminium in hair is of no value in environmental medicine. For assessment of cadmium and inorganic arsenic exposure hair analysis is only suitable as a screening method based on large populations. Monitoring of lead in hair is a valuable screening method also for small groups, especially for children. Based on toxicokinetics and under consideration of practicability the optimal biomarker of methylmercury exposure is the hair concentration. For other mercury compounds hair analysis is of lower significance. Nicotine and cotinine measurements in hair provide a practical and proper method for estimating environmental tobacco smoke exposure and to validate smoker status in epidemiological studies.

Pyrethroids are increasingly used indoors, because of their low mammalian toxicity but high insecticidal activity. Indoor application of pyrethroids, which is often carried out without adequate expert knowledge, may lead to high pesticide residues, often combined with health hazards for the people concerned. Objective of the present study is the development of a method for a biological monitoring to determine internal exposure to pyrethroids. Major pyrethroid metabolites were detected in urine by capillary gas chromatography in combination with mass selective detection (MSD). For the metabolites, the limits of determination range between 0.5 and 1 microgram/L urine. Our results so far demonstrate the detectability of cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (DVCA) and 3-phenoxybenzoic acid (3-PBA) in urine during a period of elimination of 48 hours after exposure to cypermethrin. In this paper the method is exemplary illustrated by one exposed person (pest control operator).

Over a period of three years, the frequency of the appearance of methicillin-resistant S. aureus strains (MRSA) was observed on a surgical intensive care unit. During this above-mentioned period of investigation it came to a heaped occurrence of nosocomial infections on this ICU with altogether 332 S. aureus-stems being isolated from different patient specimen. 204 (61.5%) of these were resistant against methicillin and could be divided into 48 first- and 156 follow-up-isolates. The thereupon accomplished differentiation of the 48 MRSA-first isolates by means of lysotyping and the pioneered GenePath Strain Typing System for a standardized pulsed-field-gel-electrophoresis (PFGE) gave the proof of 7 different MRSA-types. Around 7 different, in part parallel chains of infection on this ICU were observed, which could be led back to different strains. In reference to all analyzed S. aureus, an especially high rate (90%) of MRSA on this ICU could be isolated in taken wound-swabs, followed by 83.3% MRSA at catheter tips and 71,9% in tracheal and bronchial secretion. A consideration of the antibiotic susceptibility yielded, that also gentamicin and the quinolones showed an in-vitro resistance against MRSA, while fosfomycin, fusidic acid, chloramphenicol and trimethoprim/sulfamethoxazole reached positive responding rates between 80 and 100%. On the other hand, presently still 100% of the explored MRSA-strains are susceptible for glycopeptides such as vancomycin and teicoplanin. Because of intensive hospital hygienic measures the number of newly isolated MRSA could be reduced clearly on this ward.

The aim of this study was to investigate the relationship between different levels of air pollution and IgG antibody titers against tetanus toxoid in sera of 6 year old children (n = 354). Additionally, other parameters of the humoral immune response (immunoglobulins G, A, M, total IgE, complement component C3c, C-reactive protein (CRP)) were analysed. The index areas were Leipzig, Magdeburg (Saxony/Saxe-Anhalt), and Duisburg, Dortmund (Ruhr region). The control areas were Osterburg and Borken. IgG antibodies against tetanus toxoid were measured by ELISA in sera of children vaccinated three times DPT in early childhood. The other humoral parameters were measured by nephelometry. In comparison to the control area Borken the sera of children living in the index areas Duisburg and Dortmund showed a lower antibody titer. There were no differences between the index areas (Leipzig, Magdeburg) and the control area Osterburg. It has to be taken into account that the choice of Osterburg as a control area is problematic because of the lack of data on air pollution. Statistically, there was no relationship between antibody titer against tetanus toxoid and the additionally measured parameters of the humoral immune response.

Fibrogenic effects of amorphous quartz dusts are discussed more and more during recent years. In order to study alterations due to amorphous silica (quartz glass VP 203-006) in comparison with crystalline quartz (DQ-12), an inhalation experiment in rats was carried out. Male Wistar rats were separated in two dust exposed groups (n = 35) and one control group (n = 30). The experiment was carried out in inhalation chambers with a slowly rotating animal cage for 12 months, 7 h per day, and 5 days per week. The dust concentration was 10 mg/m3. After 4 and after 8 months of inhalation, 5 animals of each group were sacrificed. After 12 months 15 rats of the dust exposed groups and 10 controls were euthanized. The remaining animals were kept for another 12 months post-inhalation period. Regarding the macroscopical appearance of the lungs, the relative organ weights and the histomorphological reaction pattern, marked dust depending differences are obvious. In the lungs of DQ-12-exposed animals diffuse structural changes occur, including fibrosis and severe reaction of macrophages. Histology of lungs from quartz glass exposed animals reveals only a slight and focally arranged cellular reaction with a few collagenous fibers. However, in both dust exposed groups the mediastinal lymph nodes are extremely enlarged with severe fibroses. Additionally, the following blood parameters were determined: lysozyme, ACE, GOT, GPT, and AP. The most pronounced changes are detectable in lysozyme and GOT after DQ-12 exposure. After quartz glass exposure, the levels of these parameters are similar to the controls. These results show that the amorphous quartz tested in this experiment (quartz-glass VP 203-006) has to be considered as a compound with certain biological effects. The establishing of occupational standards seems to be justified. But, assessing the effects, the different physical and/or chemical properties of various amorphous quartz dusts have to be considered.

Es wurden die Bleikonzentrationen in den Milchschneidezahnen von 730 5–12jahrigen Schulkindern aus zwei unterschiedlich belasteten Gebieten in Nordwestdeutschland (Duisburg and Gummersbach) bestimmt. Duisburg ist ein stark industrialisiertes, hochbelastetes Gebiet, Gummersbach ein Gebiet von landlicher bis mittelstddtischer Struktur. Die Zahnbleikonzentrationen liegen im Bereich von 1,4–12,7 μg/g. Die Duisburger Kinder (N = 690) wiesen im Mittel Zahnbleikonzentrationen von 4,53 μg/g auf. Der Mittelwert der Kinder aus Gummersbach betrug 2,74 μg Pb/g. In Ubereinstimmung mit anderen Autoren wurde statistisch eine Zunahme des Zahnbleigehaltes mit dem Alter gefunden. Geschlechtsspezifische Unterschiede konnten nicht nachgewiesen wurden. Innerhalb des Stadtgebiets von Duisburg wurden die hochsten Durchschnittswerte (raumlich gleitende Mittelwerte) in der Umgebung and Hauptwindrichtung von zwei Betrieben der Bleiindustrie gefunden, wahrend die Zahnbleikonzentrationen in den ubrigen Stadtrandgebieten jedoch deutlich abnahmen. Der Zahnbleigehalt wird als Indikator der langfristigen and kumulativen Bleibelastung diskutiert, der deutlich die unterschiedlichen Expositionsbedingungen in den beiden untersuchten Gebieten reflektiert.

Sera of 72 lead workers and of 53 reference subjects were examined for levels of immunoglobulins IgM, IgG, and IgA, and complement C3 by radial immunodiffusion. Salivary IgA levels were determined in 33 lead workers and 40 reference subjects. On the average the lead workers had lower serum complement C3 and immunoglobulin levels, as well as lower salivary IgA levels, than the reference subjects. A significant negative correlation was found between blood lead concentrations (PbB) and the serum levels of complement C3 and IgG in the group of lead workers, as well as in the total population examined. However, a significant positive correlation was observed between PbB and serum IgA in the group of lead workers. The results obtained in this study are discussed in relation to numerous reports in the literature showing that lead exerts adverse effects on the immune system in animals.

A method of anti-complement immunofluorescence is described for semiquantitative measurement of antibodies in 281 sera samples obtained from patients with bronchogenic carcinoma. Tests were performed on frozen sections of 17 human bronchogenic carcinoma. - 168 sera obtained from healthy persons were used as control. Tumor and control sera were also tested on frozen sections of 10 normal lungs. - The intensity of fluorescence was measured by incident light with the aid of a Leitz microscope photometer. In comparison to control sera the mean values of fluorescence intensity of the tested 281 tumor sera were significantly higher when frozen sections of bronchogenic carcinoma were used. - In order to allow for the different content of antigens in the bronchogenic carcinoma we have calculated the rations of the tested tumor and control sera on tumor and normal sections. - The percentage of positive results showed strong dependence on the histological type of the bronchogenic carcinoma used as frozen section and differed between 16,3 and 69,1%. The highest percentage of positive reactions resulted when tumor sera were tested on frozen sections of undifferentiated bronchogenic carcinoma. Besides that sera from patients suffering from small cell bronchogenic carcinoma gave more positive results than sera from patients with other bronchogenic carcinoma. - In 78,3% of the carcinoma were tested on frozen sections of undifferentiated bronchogenic carcinoma.

These are the results of 417 primary vaccinations against smallpox with MVA, an attenuated vaccine. All of the patients were over three years old. In Europe, this group has an increased risk of postvaccinal encephalitis. The intracutaneous inoculation produced a light local infiltration and only 11.7% showed a light generalized reaction. In order to attain a reliable immunity, a second inoculation was performed one week later, epicutaneously with Elstree-vaccine. The local reaction was in general that of a normal revaccination, and 79.4% of our patients had neither fever nor general symptoms. Among the others no one became seriously ill. We did not observe any complications specific for a smallpox vaccination. In comparison to the other vaccination methods currently used, the MVA "Two-step"-vaccination is probably the safest. Its risk of a postvaccinal encephalitis is supposed to be lower according to animal experiments and theoretical considerations. This hypothesis has been confirmed meanwhile by the results of several thousand vaccinations in the already mentioned age-group.

Xenotransplants of human carcinomas were tested for consistency of the analytical data of tumor markers over several passages in nude mice and nude rats. The binding properties of antibodies against tumor-associated antigens present in sera from tumor-bearing patients were tested with aid of the anticomplement immunofluorescence. The best binding capacity was found when sera from patients with bronchogenic carcinomas reacted on xenotransplants of the digestive tract (70%). Because of the low values for controls as well as for inflammatory diseases, this test may be applicable in the early recognition of lung cancer.

209 sera of tumor-bearing patients and 133 control sera were tested by anti-complement immunofluorescence (ACIF) on 2 xenotransplants of human bronchogenic cancer and on 2 xenotransplants of rectum carcinoma passaged in nu/nu mice. Testing of sera from patients with bronchogenic carcinoma resulted in a positive reaction with the xenotransplants of bronchogenic cancer in 48.5 to 58.5%, and sera of patients with digestive tract cancer in 6.6 to 16.1%. On xenotransplants of rectum carcinoma 73.2 to 78.1% of the sera from patients with bronchogenic carcinomas and 22.6 to 29.1% of the sera of patients with digestive tract cancer reacted positively. Control sera were positive dependent on the xenotransplants in 2.0 to 12.5%. These results indicate that there are antibodies in the sera of tumor-bearing patients against one or more non organ specific tumor-associated antigen(s) occurring in an elevated concentration in carcinomas of the digestive tract than in bronchogenic carcinomas. After absorption of the sera with homogenates of bronchogenic carcinoma and liver metastases of colon carcinoma the reaction was inhibited in the ACIF, reaching control values.

We report about the occurrence and importance of antinuclear antibodies in patients with malignant diseases. - We analyzed 110 sera of patients with tumors and found in 42% ANA. In contrast a corresponding control group contained ANA in 1.8%. - Patients with bronchogenic carcinoma and those of the digestive tract possessed ANA in a comparable percentage of 36 and 39, respectively. - Sera of patients with mamma- and uteruscarcinoma contained ANA in nearly 50%. - A connection between the type of the tumor and occurrence of ANA can be assumed. - Antibodies were directed against different antigens of the nucleus, often simultaneously occurring. Antibodies which we have detected, belong to different classes of immunoglobulins (IgG, IgM and IgA). In most cases we found a combination of antibodies. In 51% of positive cases antibodies were able to fix complement.