[Epidemiology in the study of human ecology - concept and evaluation of a seminar]. / Epidemiologie im Kurs des Okologischen Stoffgebietes - Darstellung und Evaluation einer Lehrveranstaltung -

BACKGROUND: To assure proper methodology in medical studies epidemiology is the crucial profession. Medical students become acquainted with epidemiology within the course on human ecology. One year ago our department had the opportunity to assume the responsibility of this epidemiological seminar and to establish an activating teaching concept. IMPLEMENTATION: In a two hour lecture, types of epidemiologic studies, their application, typical measures, strengths and limitations are illustrated on actual examples. The basic concepts of bias, confounding and causal inference are introduced. In a two hour seminar the students read and discuss primary literature on the question "Do allergic diseases increase?" in small groups. The students present the answers on provided questions in the plenum. The results are discussed together. METHOD OF EVALUATION: At the end of each seminar within the course students rate the structural and procedural quality by means of a questionnaire. RESULTS: Compared to the former frontal teaching in epidemiology students rate the activating teaching concept significantly better in respect to lecturing style, discussion moderation, own contribution, contribution of others and course material. Comparison to the seminar "National health reporting system" (different subject, but same teaching concept and same instructor) yielded no significant differences, nor did the comparison between different instructors with the same teaching concept at the same seminar. CONCLUSIONS: The structural and procedural quality of the activating teaching concept in epidemiology is rated significantly better than the former frontal teaching concept. This difference is based on conceptual differences and not on different instructors or different subjects.

[The social security system as a topic in medical education. Own experiences and description of student's contribution]. / Das System der sozialen Sicherung als Lehrgegenstand im Medizinstudium - Erfahrungsbericht und Darstellung studentischer Beiträge -

INTRODUCTION: The special subject "sociomedicine", as defined for medical students in "items to which the written examination in the second part of the medical examination can relate" has been taught by this department for 25 years as part of the course on medical ecology. There are 4 lectures (structure of the health care system; preventive care by doctors in the community and at the place of work; introduction to health economy; introduction to epidemiology) and the following seminars in small groups: social security systems; health insurance; excursion to a rehabilitation hospital; health reporting; epidemiology. The topics are presented and taught with emphasis on didactically useful and local examples. METHODS: To ensure student participation "personal data" were introduced: Students give short reports on topics presented to them or they have to formulate questions to the topic of the seminar, questions or subjects to be dealt with. The questions concerning "social security systems" and "health insurance", collected over a 6 year period, were analyzed. RESULTS: Initially, the subject "sociomedicine" is not much appreciated by the students. The analysis shows what students think when they are challenged. The spectrum of questions mainly reflects the discussion in the media: Finance and benefits predominate, also budget and misuse, especially with reference to old-age pension and health insurance. Questions related to specific medical functions as e. g. medical expert opinion, are less often raised. However, topics such as "expansion of preventive measures", "chip card and utilisation" and "unconventional methods" are often addressed. A special demand for personal advice is seen during small talk discussions in intermissions (health insurance). CONCLUSION: The topics "medical expert opinion" and "comparison of public and private health insurance" have become positive knowledge required for the examination and for practising the medical profession. With these subjects as a starting point it appears easier for us to describe the relevant institutions and structures and the general principles of solidarity.

Laser pyrolysis products-genotoxic, clastogenic and mutagenic effects of the particulate aerosol fractions.

Laser therapy has gained wide acceptance and application in many medical disciplines. Nevertheless, during surgical procedures, the thermal destruction of tissue creates a smoke plume. Recent research data indicate that pyrolysates liberated during vaporisation of tissue induce DNA damage. However, assessing potential health hazards during medical laser treatment requires comprehensive insight into the cytotoxic, genotoxic, clastogenic and mutagenic capacity of laser pyrolysis products (LPP). Therefore, the aim of this study was to evaluate the cytotoxic, genotoxic, clastogenic and mutagenic potential of substances resulting from laser irradiation. Four different types of porcine tissues were irradiated with a surgical CO2 laser, the aerosols were sampled under defined conditions and subjected to the SCE test, micronucleus test and the HPRT test. The results showed that the pyrolysis products are strong inducers of cytotoxic effects. The pyrolysis products induced positive effects in the SCE test, micronucleus test and the HPRT test. The ability and extent to induce genotoxic and mutagenic effects turned out to be dependent on the type of tissue that had been irradiated. In general, the effects were most pronounced with liver pyrolysate. In all test systems, a clear dose relationship could be established. In conclusion, we were able to prove that the particulate fraction of laser pyrolysis aerosols originating from biological tissues undoubtedly have to be classified as cytotoxic, genotoxic, clastogenic and mutagenic. Therefore, they could be potential health hazards for humans.

["Microbial air pollutants--methods for detection of endotoxins, mycotoxins and MVOC"]. / "Mikrobielle Luftverunreinigungen--Verfahren zur Erfassung und Diagnose von Endotoxinen, Mykotoxinen und MVOC"

In the context of microbial emissions from composting facilities the methods for the detection and identification of the groups of substances released, i.e. endotoxins, mycotoxins and Microbial Volatile Compounds (MVOC) are discussed. With the aid of an overview of the different methods employed for the investigation of the single groups of compounds the current state of the art in this field is presented. In conclusion the enormous research needs, especially with regard to the mycotoxins and MVOC, are pointed out.

[Effect of microbial aerosols on the human]. / Wirkung von mikrobiellen Aerosolen auf den Menschen.

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.

Estimation of extent of cell death in different stages of normal murine hematopoiesis.

Murine hematopoiesis has been analyzed by many authors, and available data allow for quantitative evaluation of this dynamic process. In this study, the capacity of several populations of the bone marrow clonogenic cells (progenitors) to produce blood cells was compared with their actual production. The cell cycle progression rate was directly measured in the following types of hematopoietic progenitors: day 8 colony-forming units-spleen, GM-colony-forming cells, BFU-E, and CFU-E in normal mice. The cell cycle progression rates of the individual progenitors, together with their numbers in the whole hematopoietic tissue, were used to calculate the absolute numbers produced daily in each population. The data reviewed from literature were analyzed in parallel. The capacity of the progenitors to produce mature blood cells were derived from the daily production of progenitors multiplied by their clonogenic potential. This theoretical capacity to produce blood cells was compared to the actual blood cell production determined from the turnover of circulating blood elements. The comparison strongly suggested an intensive cell death rate occurring at the early stages of differentiation and its decline as the hematopoietic cells become more differentiated and mature.

[Public health fairs on "environment and human health"--participants, topics, attitudes]. / Publikumsveranstaltungen zu "Umwelt und menschliche Gesundheit"--Teilnehmer, Themen, Einstellungen.

19 meetings dealing with environment and human health, including 7 public hearings related to the planning of an incineration plant and 5 training courses for asthmatic patients, were analysed with regard to participation, persons participating in the discussions, topics covered by the remarks and also emotional involvement and standard of information. There was a total of 835 participants; 1471 "units of statements" were assessed. In the open meetings 18-33% of the participants took part in the discussion, in the closed training sessions the number was 66%. About one-third of the remarks ("units") dealt with the pollution of water, soil and air; a health risk was mentioned in about 20%. The frequency distribution of topics mentioned at the various kinds of meeting is presented. It was surprising that annoyance and anxiety were rarely expressed. The standard of information was classified rather high at the hearings concerned with the incineration of waste, and rather low at the training sessions.

Reduction of benzene toxicity by toluene.

BDF1 mice were exposed in inhalation chambers to benzene (900 ppm, 300 ppm) and/or toluene (500 ppm, 250 ppm) 6 hr per day, 5 days per week, for up to 8 weeks. Benzene alone induced a slight anemia after 4 and 8 weeks and a reduction of BFU-E and CFU-E numbers in the marrow. The coexposure to toluene reduced the degree of anemia. These results confirm previous studies where toluene was found to reduce benzene toxicity. This protective effect was most pronounced when DNA damage was studied in peripheral blood cells, bone marrow, and liver using the single cell gel (SCG) assay. With benzene alone, either with 300 or 900 ppm, a significant increase in DNA damage was detected in cells sampled from all three organs. Toluene alone did not induce a significant increase in DNA damage. The coexposure of benzene and toluene reduced the extent of DNA damage to about 50% of benzene alone. This result is considered a clear indication for a protective effect of toluene on the genetic toxicity of benzene.

Early effects of benzene exposure in mice. Hematological versus genotoxic effects.

Female BDF1 mice were exposed to 100, 300 and 900 ppm benzene 6 h/day, 5 days/week, up to 8 weeks. Hematological studies included peripheral blood data, T4 and T8 lymphocyte counts in the blood and the spleen, hemopoietic stem and progenitor cell assays in the marrow (CFU-S, CFU-C, BFU-E, CFU-E). The single cell gel assay ("comet assay") was applied in parallel with cells from the peripheral blood, bone marrow, spleen and liver. The results showed minor changes in the stem and progenitor cells and the development of a slight anemia at 4 and 8 weeks, in agreement with reported data. New was the increase of the T4/T8 ratio in the peripheral blood (not in the spleen) at the end of the first week of exposure to 300 and 900 ppm. The results of the "comet assay" indicate a much higher sensitivity to this test system (strand breaks and alkali labile sites of DNA). The tail moment indicative of the damage to DNA increased as early as 3 days with 300 ppm in the peripheral blood cells. Furthermore, the liver cells did react to a much higher extent than the other cells tested. With 100 ppm significant changes were seen in the liver after 5 days, but not in the blood. The repair, studied 24 and 48 h after the end of the exposure, was almost complete after 5-day exposure period in the blood and the liver, but not after 4 weeks of exposure with 300 ppm in the blood, and 100 and 300 ppm in the liver.

Determination of benzene metabolites in urine of mice by solid-phase extraction and high-performance liquid chromatography.

A method was developed for quantitative measurement of trans,trans-muconic acid, catechol, hydroquinone and phenol in urine. Hydrolysis of esterified and glucuronized phenolic compounds was effected by specific enzymes. The hydrolysed mixture was purified and separated by solid-phase extraction with an anion exchanger, followed by extraction with diethyl ether. By using a clean-up procedure the natural background from mouse urine could be reduced, so that the detection limit of the metabolites was in the range 3-60 mg/l. Optimization of the chromatographic conditions resulted in a short high-performance liquid chromatography analysis time. Phenol had the longest retention time of about 10 min. The clean-up procedure could also be used for phenylmercapturic acid, an additional benzene metabolite, but for sensitive high-performance liquid chromatographic detection of phenylmercapturic acid other conditions are necessary.

Hematological toxicity of tetrachloroethylene in mice.

Female C57/BL/6 x DBA/2 hybrid mice were exposed to two concentrations (270 and 135 ppm) of tetrachloroethylene (PER) in inhalation chambers for 6 h/day, 5 days per week, up to 11.5 weeks (270 ppm) and 7.5 weeks (135 ppm), respectively, followed by a 3-week exposure-free period. In the peripheral blood a reduction of lymphocytes/monocytes and of neutrophils was observed with an almost complete regeneration in the exposure-free period. A reticulocytosis during and also after the exposure indicated a compensatory reaction in the erythroid cell system. Bone marrow pluripotent stem cells (CFU-S) were not affected up to 7.5 weeks. Erythroid committed cells (BFU-E and CFU-E) did react, with a reduction of CFU-E numbers at 7.5 and 11.5 weeks. A slight reduction of CFU-C numbers at 7.5 weeks indicated, in accordance with the peripheral blood data, a disturbance of the granulocytic cell series as well.

Hematotoxic effects of benzene analyzed by mathematical modeling.

The hematopoietic cell response to benzene intoxication in mice (during and after long-term inhalation) was analyzed by a mathematical model of murine hematopoiesis. Two complementary methods, Time-Curve and Steady-State Analysis, were developed to identify target cells for benzene toxicity and to quantify the extent of damage in different stages of development of these target cells. We found that (i) erythropoietic cells were the most sensitive; (ii) granulopoietic cells were about half as sensitive as erythropoietic and (iii) hematopoietic stem cells exhibited a sensitivity that ranged between that of erythropoietic and granulopoietic cells. A dose-response relationship between benzene levels and damage in target cells (valid from 1 to more than 900 ppm) was derived that was linear for doses up to 300 ppm and plateaued thereafter. This relationship indicated that benzene-induced hematotoxicity is subject to a saturable process. Recovery of hematopoiesis following chronic benzene intoxication was simulated for different doses and preceding exposure periods. The impaired recovery following exposure periods greater than 8 weeks could be explained by a severe reduction in the maximum self-maintenance of stem cells. This study indicates that the present mathematical model represents a useful approach to investigate alternate hypotheses for the action of hematotoxic agents.

[Environment and environmental medicine--an analysis of the population's need for advice]. / Umwelt und Umweltmedizin--eine Analyse des Beratungsbedarfs der Bevölkerung.

Over a period of 6 months all inquiries related to environmental issues and environmental human health problems were recorded by the city administration (city phone, n = 71), the public health office (n = 123) and by pharmacies (n = 94). There was an institutional difference in the spectrum of the questions. Waste problems predominated at the city phone, questions related to nutrition at the pharmacies. More questions were raised by women, questioners were younger than the average population. The questions were based on own experience and on media reports to about the same extent. A relation to health complaints was presumed in 30% of the city phone calls, to about 50% at the pharmacies. Quality of the consultation was assessed by the advisors themselves.

Sensitivity of CFU-E to exogenous erythropoietin in benzene-treated mice.

Normal as well as hypertransfused BDF1 mice were exposed to 300 ppm of benzene, 6 h/day, 5 days per week for 2, 4, and 6 weeks respectively. Erythroid-committed hematopoietic progenitor cells CFU-E were determined in the bone marrow, and 59Fe incorporation was measured in the peripheral blood 48 h after its injection, as an indicator of active erythroid cell production. CFU-E numbers were reduced in benzene-exposed mice at all intervals, as was 59Fe incorporation in the peripheral blood after 2 weeks of exposure. In hypertransfused mice the CFU-E suppression, caused primarily by the hypertransfusion, was aggravated by benzene. After injection of 1 IU Ep 4 days before killing the CFU-E numbers and the 59Fe incorporation increased in controls as well as in benzene-exposed animals, but the difference persisted. After nine consecutive Ep injections the difference concerning the femur disappeared after 2 and 6 weeks of benzene exposure but was still present in the peripheral blood. These results suggest that chronic benzene exposure has a negative effect on early erythroid-committed, Ep-responsive hematopoietic cells.

Action of benzene metabolites on murine hematopoietic colony-forming cells in vitro.

Five benzene metabolites--phenol, catechol, hydroquinone, parabenzoquinone, and trans,trans-muconaldehyde--were tested in vitro in murine hematopoietic cell cultures for erythrocytic (BFU-E and CFU-E) and granulocytic (CFU-C) colony growth. The dose range was 4 x 10(-4) to 4 x 10(-8) M. Of these compounds, phenol showed the lowest toxicity. In general, CFU-E cultures were far more sensitive than CFU-C and BFU-E. The results are discussed in relation to the test system used, the in vivo sensitivity of CFU-E, and the lack of knowledge about in vivo concentrations of these compounds.

Thymic nurse cells: differentiation of thymocytes within complexes.

Thymic nurse cell complexes (TNC-c) were isolated from thymuses of BDF1 mice at pre-determined intervals during the 12-week latency period that precedes the development of leukemias. T-cell leukemias were induced by a single i.v. injection of 50 mg/kg of methylnitrosourea (MNU). In order to clarify processes taking place in TNC-c, the complexes of mice after MNU injection were compared with TNC-c of age-matched control mice, with respect to their number per thymus, the distribution of TNC-c according to their size (the number of intra-TNC thymocytes reflects the type of TNC-c), the number of intra-TNC thymocytes that undergo DNA synthesis, and the phenotype of thymocytes inside TNC-c. During the latency period of leukemogenesis, the effects of MNU were shown to involve, in addition to changes in number of TNC-c, a decrease in the number of thymocytes incorporating labeled thymidine, viz., the number of dividing cells, thus affecting the size distribution of TNC-c types. Intra-TNC thymocytes of control mice were heterogeneous in their phenotype and represented cells at varying stages of their maturation cycle. MNU administration was followed by selective differentiation of thymocytes within TNC-c to Lyt 1-thymocytes in some and to Lyt 2-thymocytes in others. Lyt 1 and Lyt 2 being specific antigens expressed by thymocytes.

Effect of benzene on fibroblastoid colony-forming units in mice.

After exposure of C57BL6 x DBA/2 mice to benzene in air their number of bone marrow fibroblastoid precursor cells, CFU-F, was determined. The CFU-F exhibited an increasing plating efficiency, giving rise to a larger number of colonies and to colonies of greater size. This effect was dose dependent. When the mice were exposed for 16 weeks and were then allowed to rest, their CFU-F plating efficiency returned to normal within 6 weeks, but then increased again. Hematopoietic stem cells, such as CFU-S and CFU-C exhibited a dose-dependent depression. The in vitro exposure of bone marrow cells to benzene metabolites resulted in a dose-dependent depression of CFU-F numbers.

[Comparative studies of the effectiveness of brief psychotherapy, acupuncture and papaverin therapy in patients with irritable bowel syndrome]. / Vergleichende Untersuchungen zur Effektivität der kleinen Psychotherapie, der Akupunktur und der Papaverintherapie bei Patienten mit Colon irritabile.

At a comparison among 5 therapy methods the small psychotherapy with a success-rate of 74% is high-significantly more prosperous than the other examined methods. The acupuncture with 31% long-term success is significantly superior to the pseudoacupuncture (17.2%). The papaverine therapy results in a long-lasting status free of symptoms in 17.2% of the patients and is significantly different from the results of the papaverine-placebo-therapy (0%). Distinct differences in the success-rates of the small psychotherapy with different therapists prove the role of the personality and the perfection in mastering the methods with psychotherapeutic procedures. Comparable differences between the examiners were not found among the effects of a spasmolytic therapy.

The influence of ethanol on the stem cell toxicity of benzene in mice.

BDF1 mice were exposed to 100, 300, and 900 ppm benzene vapor, and the numbers of hematopoietic progenitor cells, early and late erythroid progenitors (BFU-E and CFU-E) and granuloid progenitors (CFU-C), were determined with and without additional exposure to ethanol (5, 10, 15 vol%) in the drinking water. The duration of benzene inhalation was up to 4 weeks, 6 hr per day, 5 days per week. It was shown that the number of CFU-E per femur was depressed in a dose-dependent manner by benzene alone and also by ethanol combined with a given benzene concentration. CFU-E showed rapid regeneration after the end of the exposure, but not BFU-E and CFU-C. Prolongation of the ethanol exposure after withdrawal of benzene had only a marginal effect on progenitor cell regeneration.

Ferrokinetics and erythropoiesis in mice after long-term inhalation of benzene.

Ferrokinetics and erythropoiesis were examined in mice exposed for 6 or 7 weeks to an airborne concentration of 300 ppm of benzene, for 6 h per day, and 5 days per week. Ferrokinetic indicators showed only a slightly enhanced production of haeme and erythrocytes in the spleen (133% +/- 18% and 122% +/- 17%, respectively). Production did not change in the femoral marrow; a decline of CFU-C, BFU-E and especially CFU-E (34% +/- 8%) took place there and a shift of cellularity into less mature developmental classes in the erythroblast compartment, without this compartment as a whole being damaged. The erythrocytes produced have an enhanced MCV (109% +/- 0%) and MCH (109% +/- 1%) with an unchanged MCHC; their concentration in blood sank to 87% +/- 1%. The absolute reticulocyte count rose to 160% +/- 16%. 59Fe incorporation into the liver declined far below the level attributable to decreased accessibility of the tracer (84% +/- 4%). A shortening of the life span of late erythroblasts and circulating erythrocytes was deduced from these findings and methodological problems related to some of the seemingly controversial findings are discussed.