Observation of the Self-Modulation Instability via Time-Resolved Measurements.

Self-modulation of an electron beam in a plasma has been observed. The propagation of a long (several plasma wavelengths) electron bunch in an overdense plasma resulted in the production of multiple bunches via the self-modulation instability. Using a combination of a radio-frequency deflector and a dipole spectrometer, the time and energy structure of the self-modulated beam was measured. The longitudinal phase space measurement showed the modulation of a long electron bunch into three bunches with an approximately 200 keV/c amplitude momentum modulation. Demonstrating this effect is a breakthrough for proton-driven plasma accelerator schemes aiming to utilize the same physical effect.

[Uncertainty analysis of quantitative risk assessment in temporally variable exposures: model observations based on biological and epidemiological risk models]. / Unsicherheitsanalyse für quantitative Risikoabschätzungen bei zeitlich variablen Expositionen: Modellbetrachtungen auf Grundlage biologischer und epidemiologischer Risikomodelle.

Unit risks used for quantitative cancer risk assessment are defined for constant lifetime exposures. The condition of temporal stability, however, usually is not fulfilled in environmental health applications. In practice, cancer risks for time-dependent exposures are often estimated by calculating lifetime average exposure, assuming a mean life expectancy of 70 years. In the present paper we discuss the question whether this is an appropriate procedure considering various variants of multi stage and epidemiological relative risk models. For this purpose, lifetime risks for time dependent exposures as calculated according to the respective model assumptions, were compared with lifetime risks estimated by the lifetime average exposure approach. As typical exposure histories in environmental health applications we studied exposures either limited to the first 5 years of life (children scenario) or limited to duration of employment (30th to 65th year of age; occupational scenario). The consideration of multistage models (Armitage-Doll- and Moolgavkar-Venzon-Knudson model) in general would not induce serious bias in risk estimation when exposures are limited to middle ages (occupational scenario). On the other hand, when exposures occur only in very young ages or only in very old ages the risk estimated by using lifetime average exposure is not comparable with the predictions of multistage models. Whereas the degree of possible underestimation is bounded by factors well below 10, the amount of possible overestimation is unbounded and may become arbitrarily high, when exposures concentrate in extreme ages. In a second part of the study we investigated different relative risk models, taking lung cancer as an example. The models differed with respect to assumptions on latent periods and moderating effects of age at exposure and age at risk. The simulations showed that the unit risk concept is appropriate for the occupational scenario. For the children scenario results strongly depend on the assumptions made. Whereas the degree of possible underestimation is acceptable, in some models the degree of possible overestimation may become arbitrarily high. Both parts of the study showed that bias induced by using lifetime average exposure is acceptable when exposures are limited to middle ages. On the other hand, the unit risk concept should not uncritically be applied to exposures limited to early childhood (e.g., in kindergartens or due to mouthing activities). Depending on the assumptions made, lifetime risk may either be moderately underestimated or grossly overestimated. Without additional knowledge on mechanisms or latency period risk estimations are of questionable value. With respect to exposures in childhood regulation should concentrate on initiating substances or substances known to have long latent periods, respectively. With respect to cancers which occur relatively frequent already in childhood specific considerations are recommended.

[Aviation fuels and aircraft emissions. A risk characterization for airport neighbors using Hamburg Airport as an example]. / Flugzeugtreibstoffe und Flugzeugemissionen. Eine Risikocharakterisierung für Flughafenanwohner am Beispiel des Hamburger Flughafens.

Aviation fuels are well characterised regarding their physical and chemical properties. Health effects of fuel vapours and of liquid fuel are described after occupational exposure and in animal studies. Exposure of the general population (airport visitors and people living in the vicinity of airports) may occur during fuel supply particularly in warm summers (odour). Aircraft emissions vary with the engine type and the kind of fuel. Combustion of aviation fuel results in CO2, H2O, CO, C, NOx and a great number of organic compounds. Among the emitted polyaromatic hydrocarbons (PAH) no compound characteristic for jet engines (tracer) could be detected so far. Hardly any data exist on the toxicology of jet engine emissions. According to analyses of their chemical composition, however, they contain various toxicologically relevant compounds including carcinogenic substances. Measurements in ambient air around the Hamburg Airport show no elevated pollutant levels. However, no such data exist on aldehydes, black smoke or fine particles. Annoying odours have been stated in some areas around the airport, which were mainly attributed to the aircraft engine emissions rather than to fuel vapours.

[Evaluation and requirements of natural room ventilation]. / Beurteilung und Erfordernisse der natürlichen Raumlüftung.

The current application of the carbon dioxide standard ("Kohlensäuremassstab") of 0.1 vol.-% CO2 given by Pettenkofer 140 years ago is assessed in order to evaluate tolerable indoor air and sufficient indoor air ventilation. For this purpose, criteria by Pettenkofer were contrasted by currently valid criteria. It was found that an actual guidance value should be clearly higher than the one given by Pettenkofer. As confirmed by recent measurements this actual guidance value should be around 0.15 vol.-% CO2. By means of a few examples requirements for indoor aeration of living rooms and classrooms are made evident. The corresponding calculations are based on the indoor air guidance value (i.e. actualised value of Pettenkofer) of 0.15 vol.-% CO2 and are based on respiration rates compiled in "Standards of exposure assessment" by the health authorities of the German federal states. The calculated number of complete renewals of air achieved by circulation shows that recent values given by others concerning the permitted indoor self aeration were set too low and require correction. Applying the demonstrated requirements for indoor ventilation many of the well known problems of indoor air can be minimised or even solved.

2,2',4,4',5,5'-hexabromobiphenyl: its toxicokinetics, biotransformation and porphyrinogenic action in rats.

The porphyrinogenic action of 2,2',4,4',5,5'-hexabromobiphenyl and its toxicokinetics were studied in female Wistar rats that were treated every other day for 6 wk with oral doses of 112 mg/kg body weight. Subsequently, the animals were kept for a further period of 22.5 months but without supply of the brominated biphenyl. 10.5 months after cessation of treatment the compound reached a maximum concentration in the adipose tissue followed by a gradual decline of its content. In the liver the concentration of the substance started to decrease 3 months after cessation of treatment. In the excreta, hexabromobiphenylol and two pentabromobiphenyls were detected as metabolites. The rate of biotransformation amounted to about 5%. At the end of the dosing period no alterations in the content and profile of the hepatic porphyrins were observed. Urinary porphyrins and their precursors delta-aminolaevulinic acid and porphobilinogen were slightly elevated. The urinary porphyrin pattern and faecal porphyrin content and pattern did not differ from those of the controls. 15 and 18 months after cessation of treatment (16.5 and 19.5 months after the start of treatment) two animals were found to have marked alterations in the content and profile of hepatic porphyrins with uro- and heptacarboxyporphyrin predominating. It was concluded that there is an extreme delayed individual porphyric response to 2,2',4,4',5,5'-hexabromobiphenyl in female rats.

CCK-8 and gastrin plasma levels in cholecystectomized and colorectal cancer patients.

The elevated incidence of large bowel carcinoma after cholecystectomy has long been controversial. The pathomechanism of this entity, however, is still unclear. Many authors have demonstrated a correlation between cholecystokinin (CCK) and gastrin levels and the occurrence of colorectal cancer. As yet, no clear data are available on the potential impact of cholecystectomy on CCK level alterations. Moreover, no reports have yet been published on CCK receptors. We have investigated the role of CCK-8 and gastrin plasma levels in patients with prior cholecystectomy and CCK receptor levels in patients with colorectal cancer. 125 patients entered a prospective study. Of these, 45 served as controls. 40 patients had prior cholecystectomy, 5 patients underwent cholecystectomy during the ongoing trial. 35 patients had a colorectal cancer, 5 of these had prior cholecystectomy. No patient had elevated CCK-8 plasma levels. Gastrin levels were slightly elevated in 2 patients. There was no correlation between large bowel carcinoma and CCK-8 and gastrin levels. Elevated CCK-8 levels following cholecystectomy occur neither immediately after surgery nor on a long-term basis. Immunohistochemical studies in patients with colorectal cancer showed no CCK receptors in the normal colonic or tumor tissue. These findings are contrary to gastrin receptor data.

Hexaclorobenceno y pentacloro fenol en tejido adiposo y orina de un nino con porfiria cutanea tardia: evaluacion del tratamiento(s-adenosil-L-metionina y bajas dosis de cloriquina): a cuatro anos de inicido el mismo / Hexaclorobenzene and poentachlorophenol in fatty tissue and urine of child with porfiria cutanea tarda. Treatment evaluation (S-Adenosyl-L-Methionine and low dose of Chloroquine) four years after

Se ha estudiado el contenido de hexaclorobenceno(HCB) y pentaclorofenol(PCP)en tejido adiposo y orina de un ninio con porfiria cutanea tardia (PCT) hereditaria y del producto quimico con el cual estuvo en contacto. El contenido de HCB (2,3 ug/g) en orinayPCF (5,0 ml) fueron elevados respectoa los valores normales (HCB tej. adiposo<1 ug/gyPCF urinario ,0,1 ng/ml). L presencia de PCF en orina,indicador de intoxicacion por HCB,esta sugiriendo que este policlorado fue el desencadenante de la PCT en este ninio portador de la enfermedad. La variacion del contenido de porfirinas urinarias durante los tratamientos con A)bicarbonato (10mg/dia)y B) conbinado:S adenosil-L-Metionina(SAM)(12mg/kg/diax20dias) y cloroquina(2x110mg/semana) mostraron: En A)disminucion del 50 por ciento de las porfirinas iniciales (1700 ug/24h) luego de 50 meses de tratamiento,B) disminucion hasta alcanzar los valores normales(20-250 ug/24 h) luego de 4 meses de tratamiento. Las porfirinas se mantuvieron en valores normalesaun hasta 4 anios de iniciada la terapia con SAM y cloriquina

Hexaclorobenceno y pentacloro fenol en tejido adiposo y orina de un nino con porfiria cutanea tardia: evaluacion del tratamiento(s-adenosil-L-metionina y bajas dosis de cloriquina): a cuatro anos de inicido el mismo / Hexaclorobenzene and poentachlorophenol in fatty tissue and urine of child with porfiria cutanea tarda. Treatment evaluation (S-Adenosyl-L-Methionine and low dose of Chloroquine) four years after

Se ha estudiado el contenido de hexaclorobenceno(HCB) y pentaclorofenol(PCP)en tejido adiposo y orina de un ninio con porfiria cutanea tardia (PCT) hereditaria y del producto quimico con el cual estuvo en contacto. El contenido de HCB (2,3 ug/g) en orinayPCF (5,0 ml) fueron elevados respectoa los valores normales (HCB tej. adiposo<1 ug/gyPCF urinario ,0,1 ng/ml). L presencia de PCF en orina,indicador de intoxicacion por HCB,esta sugiriendo que este policlorado fue el desencadenante de la PCT en este ninio portador de la enfermedad. La variacion del contenido de porfirinas urinarias durante los tratamientos con A)bicarbonato (10mg/dia)y B) conbinado:S adenosil-L-Metionina(SAM)(12mg/kg/diax20dias) y cloroquina(2x110mg/semana) mostraron: En A)disminucion del 50 por ciento de las porfirinas iniciales (1700 ug/24h) luego de 50 meses de tratamiento,B) disminucion hasta alcanzar los valores normales(20-250 ug/24 h) luego de 4 meses de tratamiento. Las porfirinas se mantuvieron en valores normalesaun hasta 4 anios de iniciada la terapia con SAM y cloriquina

2,2',3',4,4'5,5'-Hepatachlorobiphenyl (PCB 180)--on its toxicokinetics, biotransformation and porphyrinogenic action in female rats.

The toxicokinetics and biotransformation of 2,2',3',4,4',5,5'-heptachlorobiphenyl, as well as its influence on the activity of microsomal and cytosolic enzymes and on the porphyrin pathway in the liver were studied in female rats following oral treatment with 7 mg/kg every other day for 3 months. One day after cessation of treatment the concentration of the compound in liver, spleen, CNS and blood was 100-500 times and in the trachea it was only 5 times less than in the adipose tissue. The daily excretion with the feces and urine amounted to 35 and 1.5 micrograms, respectively. In both excreta, heptachlorobiphenylol was identified as a metabolite. The biotransformation rate was estimated to be about 5%. Investigations of the liver revealed increases in the relative liver weight, total cytochrome P-450 content, O-deethylation of 7-ethoxycoumarin and in the activity of glutathione S-transferases. Disturbances of the hepatic porphyrin pathway were not detected. Only at the end of a post-dosing period of 12 months did the hepatic uroporphyrinogen decarboxylase show diminished activity. Only one of these animals with diminished enzyme activity showed drastically elevated porphyrins. In these animals, the fecal and urinary porphyrins did not differ from controls. At no time did heptachlorobiphenyl influence the urinary excretion of delta-aminolevulinic acid and porphobilinogen. The results indicate 1) that this congener shows expected toxicokinetics with the exception of being accumulated in the trachea and 2) that this congener induces disturbances of the hepatic porphyrin pathway several months after cessation of treatment.

Disseminated histoplasmosis in AIDS patients in Maryland.

These patients demonstrate the difficulty in arriving at the diagnosis of disseminated histoplasmosis. The diagnosis in two of the three patients also served as the initial AIDS case-defining opportunistic infection. In each of these patients, the clinical presentations were atypical and in only one patient was a positive exposure history elicited. Recurrent bowel obstruction was the presenting complaint in the first patient and the diagnosis was made only on pathologic exam of the resected small bowel. The second patient's diagnosis was made on biopsy of the colon via colonoscopy. The third patient's diagnosis also eluded an extensive FUO workup; he was diagnosed by bone marrow culture and silver stain of a mediastinal lymph node biopsy, despite serial negative serologic tests for histoplasmosis. The first two patients had significant gastrointestinal disease which is a relatively unusual manifestation for disseminated histoplasmosis. The third patient illustrates the limited diagnostic usefulness of serologic testing in AIDS patients and the continued usefulness of bone marrow analysis in an FUO evaluation. In conclusion, these case presentations demonstrate that disseminated histoplasmosis in patients with HIV infection can present with unusual manifestations, outside of the typical endemic arca, without a positive exposure history or positive serologic test, and may be the initial AIDS case-defining opportunistic infection in these patients. Consequently, a disseminated histoplasmosis should be considered in all AIDS patients with perplexing clinical presentations.

The hepatic glutathione content and glutathione S-transferase activity in the pike (Esox lucius L.) and rat.

1. The content of glutathione and glutathione disulfide and the activity of the glutathione S-transferase were determined in the liver of pike and rat. 2. It was found that the liver of pike contains far less glutathione than the liver of rats, while the glutathione disulfide content was similar in both species. 3. The activity of the hepatic glutathione S-transferase was more effective in pike than in rats.

[The value of 2 distinct prognosis scores in patients with peritonitis. The Mannheim Peritonitis Index versus the Apache II score]. / Unterschiedliche Aussagekraft von zwei verschiedenen Prognose-Scores bei Patienten mit Peritonitis. Mannheimer Peritonitis-Index versus Apache II-Score.

Seventy patients suffering from purulent peritonitis entered this study, 31 of them were taken in prospectively, to contrast two different prognostic scores, the Mannheim Peritonitis Index (MPI) vs. the Apache II (APS II). The MPI is shown as a prognostic index for peritonitis with high accuracy in individual prognosis. The simultaneous use of both scores, the MPI as well as the APS II, leads to a negligible improvement of prognostic accuracy. Moreover, sensitivity and specificity with the MPI are of higher accuracy than calculated with the APS II.

[Organic-chemical air pollutants indoors--aspects of environmental toxicologic evaluation]. / Organisch-chemische Luftverunreinigungen in Innenräumen--Aspekte der umwelttoxikologischen Beurteilung.

Indoor air pollution is characterized by a wide range of concentrations of many, mainly organic substances. To avoid adverse health effects it is necessary to develop indoor air quality standards. Standards should reflect the way and time of exposure and the fact that health risks might be possible especially to sensitive people. The toxicological basis for regulating indoor air quality is discussed. Special attention is given to organic substances with a cancerogenic and accumulating potential. An approach in setting standards of indoor air quality for frequent organic substances like toluene, xylene, styrene, dichloromethane, 1.1.1-trichloroethane, trichloroethene, tetrachloroethene, pentachlorophenol and PCB is presented, incorporating adequate protection margins. The results of this approach are compared with the WHO air quality guidelines and the German MIK values.

Human risk assessment of carcinogens from an administrative perspective.

For evaluation of the carcinogenic potency of an environmental chemical or a mixture of chemicals, epidemiological or workplace studies, animal studies, and in vitro tests are the three major strategies used. Asbestos fibers and 1,2-dichloroethane are chosen as examples. They illustrate that the strategies may enable the implementation of measures by health authorities.

[Health effects of ozone as component of summer smog]. / Gesundheitliche Wirkungen des Ozons als Bestandteil des Sommersmogs.

During the sunny summers of 1989 and 1990 in Germany the outdoor ozone levels repeatedly exceeded the value of the air quality guidelines proposed by the World Health Organization. Both in multiple sites within industrial polluted and in supposedly clean outside areas the ozone concentrations exceeded the value of 180 micrograms/m3. The following paper is intended to contribute to an understanding of the health effects of ozone. It compiles data and views on the formation and analysis of ozone, on its distribution as ambient ground level pollutant, on respiratory and common symptoms in man and on the toxicokinetics, responses and pathogenesis in experimental animals. Studies on healthy exercising adult volunteers exposed to 240 micrograms/m3 ozone in purified lab air or in ambient air revealed a significant influence on connections between forced vital capacity, forced expiratory volume, flow rate and peak expiratory flow rate and the pollutant. Exposure to lower ozone levels induced the same effects, but they were of smaller magnitude. Children aged 8-15 years exercising under field conditions showed decrements in lung function even at ozone levels well below 200 micrograms/m3. Restitution of lung function needs periods of several days, although the induction of effects is a matter of hours. The relevance of the transient pulmonary responses is widely unclear. Among patients with chronic obstructive pulmonary disease or asthma, the functional responsiveness to ozone is not greater than among healthy subjects. Interindividual differences in responsiveness occur but are not predictable. Information on chronic effects is rather limited.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions of heterocyclic Maillard products with the hepatic microsomal monooxygenase system.

1. Interactions of methyl-substituted pyrazines, and other constituents of Maillard products generated during heat treatment of food, with hepatic microsomal mixed-function oxygenases were studied in vitro. 2. Spectral interactions of N-containing heteroaromatic compounds with the cytochrome P-450 system are type I or type II depending on the state of induction, and are relatively weak. Inhibition of 7-ethoxycoumarin O-deethylation by these compounds is ten times lower than that of metyrapone, agreeing with the weak spectral interaction. Inhibition is competitive for 2,3-dimethylquinoxaline, and complex for 2,5-dimethylpyrazine and 2,3,5,6-tetramethylpyrazine. 3. Spectral and inhibitory interactions indicate biotransformation. This was studied with 2,3,5,6-tetramethylpyrazine; the metabolite formed was identified as 2-hydroxymethyl-3,5,6-trimethylpyrazine. Metabolism to the N-oxide did not occur.

Inhibitory effect of tetrachloro-p-hydroquinone and other metabolites of hexachlorobenzene on hepatic uroporphyrinogen decarboxylase activity with reference to the role of glutathione.

Exposure of rats to HCB caused a dose-dependent depletion of GSH. Chlorophenolic and sulfur-containing metabolites of HCB incubated with GSH-free rat liver cytosolic protein drastically diminished the UROD activity. In addition, HCB also exhibited inhibitory potency. The most effective compounds studied were TCH and its oxidation product, chloranil. Incubation of liver cytosolic protein and of GSH with HCB and its metabolites yielded results that suggested interaction between the compounds and cell constituents--an interaction that may cause inhibition of the hepatic UROD activity in the HCB-exposed organism.

Elimination of porphyrins and their precursors in rats pretreated with hexabromobenzene.

The elimination times of porphyrins and their precursors and of hexabromobenzene (HBB) itself were studied in female rats given 15 mg HBB by stomach tube every other day for 4 months. The concentrations of HBB in the blood, liver and adipose tissue were in the ratio 1:1.5:25, 24 hr after the last dose. Two weeks after the end of treatment, HBB was no longer detectable in the tissues. In animals given a single oral dose of 16.6 mg HBB/kg body weight, HBB was no longer detectable in adipose tissue 12 days after dosing. The half-life of HBB in adipose tissue was about 2.5 days in the animals given HBB for 4 months, and at the end of the treatment the concentrations of porphyrin in the liver, urine and faeces were increased to about 1000, 600-700 and 60-70 times the control values. The amounts of delta-aminolaevulinic acid and porphobilinogen in the urine of treated animals were 6-7 times those in controls. After the end of HBB treatment, it took almost 1.5 yr for delta-aminolaevulinic acid and porphobilinogen excretion to return to normal. Nearly 2 yr were needed for complete elimination of the accumulated liver porphyrins.

Screening for the ability of hexachlorobenzene metabolites to decrease rat liver porphyrinogen carboxy-lyase.

In order to examine inhibitory effects of hexachlorobenzene metabolites on the hepatic porphyrinogen carboxylyase activity, rat liver cytosol was incubated with uroporphyrinogen III and chlorinated phenols, thiophenols, thioanisoles and benzenes. Then, the occurrence of hepta-, hexa-, penta- and tetracarboxyporphyrinogen = coproporphyrinogen (measured as porphyrins) was determined. Inhibitory effects were exerted by tetrachlorohydroquinone, pentachlorophenol, pentachlorothiophenol, 1,2,3,5- and 1,2,4,5-tetrachlorobenzene. Other compounds including hexachlorobenzene which was tested for comparative reasons did not impair uroporphyrinogen decarboxylation. In the presence of tetrachlorohydroquinone, uroporphyrinogen merely was decarboxylated to hepta- and hexacarboxyporphyrinogen. Under the influence of the other 4 compounds with inhibitory effects, pentacarboxyporphyrinogen and coproporphyrinogen were formed additionally. Coproporphyrinogen formation was inhibited completely by tetrachlorohydroquinone, while pentachlorophenol diminished its formation by about 50% and pentachlorothiophenol, 1,2,3,5- and 1,2,4,5-tetrachlorobenzene by less than 10%.

Excretion of metabolites of hexachlorobenzene in the rat and in man.

From the urine of rats treated with hexachlorobenzene (HCB), 21 metabolites were separated by capillary gas chromatography. Sulfur-containing metabolites were present in larger numbers and greater amounts than phenolic compounds. In studies on the origin of pentachlorophenol in man, HCB was determined in adipose tissue and pentachlorophenol in urine, and in 48 out of 60 females, 80-90% of the daily urinary pentachlorophenol appeared to be formed from HCB.