Towards virtual histology with X-ray grating interferometry.

Breast cancer is the most common type of cancer worldwide. Diagnosing breast cancer relies on clinical examination, imaging and biopsy. A core-needle biopsy enables a morphological and biochemical characterization of the cancer and is considered the gold standard for breast cancer diagnosis.

Effects of the genotoxic compounds, benzo[a]pyrene and cyclophosphamide on phase 1 and 2 activities in EpiDerm™ models.

The micronucleus assay in the 3D human reconstructed EpiDerm™ skin model (RSMN) is a promising new assay for evaluating genotoxicity of dermally applied chemicals. To complement the testing of metabolically activated chemicals, such as cyclophosphamide (CPA) and benzo[a]pyrene (B[a]P), we measured phase 1 (ethoxyresorufin O-deethylation (EROD) and testosterone metabolism) and 2 activities (UGTs and GSTs) in non-treated and genotoxin treated EpiDerm™ models in a study design which mimics the RSMN assay. The assay involved a three-dose dosing regimen over 72 h to take into account effects e.

Oxidant generation and toxicity of size-fractionated ambient particles in human lung epithelial cells.

Exposure to ambient particulate matter (PM) is associated with respiratory and cardiovascular disease and lung cancer. In this study, we used size fractionated PM samples (3-7, 1.5-3, 0.

Dose dependence of oral tolerance to nickel.

The dose dependence of oral nickel tolerance was analyzed by comparing three different subsets of C57BL/6 mice: Ni(very low) mice were reared in a nickel-reduced environment, Ni(low) and Ni(high) mice were reared in a stainless steel-containing environment and the latter received oral NiCl(2) (10 mM). In spleen and feces, Ni(very low) mice exhibit significantly lower nickel concentrations than Ni(low) and Ni(high) mice. In contrast to Ni(very low) mice that can be sensitized with a single intradermal administration of NiCl(2) alone, Ni(low) mice can only be sensitized in the presence of an adjuvant and Ni(high) mice cannot be sensitized at all.

Formation of PAH-DNA adducts after in vivo and vitro exposure of rats and lung cells to different commercial carbon blacks.

Objective: The current study was designed to test the possible release and bioavailability of polycyclic aromatic hydrocarbons (PAHs) from a set of commercial carbon blacks (CBs) as well as the ability of these PAHs to form bulky DNA adducts.

Methods: In four commercial CBs (Printex 90, Sterling V, N330, Lampblack 101), leaching of PAH was examined through (1) release of parent PAHs in saline with or without surfactant, and (2) PAH adducts in lung epithelial cells (A549) or in rat lungs after exposure to two CBs (Printex 90, Sterling V) for 13 weeks (50 mg/m(3)). In vitro experiments were done with original and extracted particles, as well as organic extracts of CB in DMSO.

Determination of selected microbial volatile organic compounds by diffusive sampling and dual-column capillary GC-FID--a new feasible approach for the detection of an exposure to indoor mould fungi?

A new, analytically valid procedure is described to assess the exposure of human beings to the so-called microbial volatile organic compounds (MVOCs) in air. The method can be used routinely for large sample numbers and is especially valuable as a basis for further research on the correlation between single MVOCs and indoor mould growth. The procedure is based on the fact that fungi produce a variety of volatile organic compounds, such as 3-methylbutan-1-ol, 3-methylbutan-2-ol, fenchone, heptan-2-one, hexan-2-one, octan-3-one, octan-3-ol, pentan-2-ol, alpha-terpineol, and thujopsene, which they emit into the indoor environment.

Yttrium-90 DOTATOC: first clinical results.

In a pilot study, DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTATOC), which can be labelled with the beta-emitting radioisotope yttrium-90, has recently been used for the treatment of patients with advanced somatostatin receptor-positive tumours who had no other treatment option. The aim of the present study was to elucidate the therapeutic potential of (90)Y-DOTATOC in a larger number of patients employing a standardized treatment protocol. Careful attention was paid to any side-effects (renal and/or haematological toxicity).

Loco-regional radioimmunotherapy of high-grade malignant gliomas using specific monoclonal antibodies labeled with 90Y: a phase I study.

A Phase I radioimmunotherapy trial was conducted in which radioconjugated monoclonal antibody (MAb) was directly infused into the tumor or postoperative tumoral bed in patients with high-grade malignant glioma. BC-4, a murine MAb that recognizes tenascin, was used in these studies. The MAb was labeled with 90Y, a pure beta emitter with maximum energy of 2.

Biokinetics and dosimetry in patients administered with (111)In-DOTA-Tyr(3)-octreotide: implications for internal radiotherapy with (90)Y-DOTATOC.

Recent advances in receptor-mediated tumour imaging have resulted in the development of a new somatostatin analogue, DOTA-dPhe(1)-Tyr(3)-octreotide. This new compound, named DOTATOC, has shown high affinity for somatostatin receptors, ease of labelling and stability with yttrium-90 and favourable biodistribution in animal models. The aim of this work was to evaluate the biodistribution and dosimetry of DOTATOC radiolabelled with indium-111, in anticipation of therapy trials with (90)Y-DOTATOC in patients.

Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas.

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am.

Determination of benzene, toluene, ethylbenzene and xylenes in indoor air at environmental levels using diffusive samplers in combination with headspace solid-phase microextraction and high-resolution gas chromatography-flame ionization detection.

An improved analytical method for passive air sampling is presented based on a combination of commercially available diffusive samplers with headspace solid-phase microextraction and high-resolution gas chromatography with flame ionization detection (HRGC-FID). This procedure is targeted for short-term BTEX (benzene, toluene, ethylbenzene and o-, m- and p-xylenes) determinations at environmental concentrations and can be applied for sampling intervals between 30 min and 24 h. The analytes are adsorbed onto the charcoal pad of a passive sampler and then extracted with carbon disulphide-methanol.

Determination of physiological levels of volatile organic compounds in blood using static headspace capillary gas chromatography with serial triple detection.

A static capillary gas chromatographic method using three different detectors [photoionization detector (PID), electron capture detector (ECD) and flame ionization detector (FID)] switched in series is presented for the determination of volatile organic compounds (VOCs) in sub microgram l-1 levels. The method was applied for the analysis of selected environmentally and occupationally relevant non-halogenated and chlorinated aromatic hydrocarbons (e.g.

DOTATOC: a powerful new tool for receptor-mediated radionuclide therapy.

This study presents the first successful use of a peptidic vector, DOTATOC, labelled with the beta-emitting radioisotope yttrium-90, for the treatment of a patient with somatostatin receptor-positive abdominal metastases of a neuroendocrine carcinoma of unknown localization. Tumour response and symptomatic relief were achieved. In addition, the new substance DOTATOC was labelled with the diagnostic chemical analogue indium-111 and studied in three patients with histopathologically verified neuroendocrine abdominal tumours for its diagnostic sensitivity and compared with the commercially available OctreoScan.

Biodistribution of 111In-labelled SCN-bz-DTPA-BC-2 MAb following loco-regional injection into glioblastomas.

We analyzed the biodistribution of the 111In-labelled murine anti-tenascin-C MAb BC-2 after intralesional injection in 15 glioblastoma patients. The activated ligand DTPA was conjugated via the isothiocyanato-benzyl group onto BC-2. Conjugates were labelled with 111In, displaying immunoreactivity greater than 90% and labelling efficiency of 99 +/- 1%.

Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1,Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy.

In vitro octreotide receptor binding of [111In-DOTA0,d-Phe1, Tyr3]octreotide (111In-DOTATOC) and the in vivo metabolism of 90Y- or 111In-labelled DOTATOC were investigated in rats in comparison with [111In-DTPA0]octreotide [111In-DTPAOC). 111In-DOTATOC was found to have an affinity similar to octreotide itself for the octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of 90Y- or 111In-labelled DOTATOC, uptake of radioactivity in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2-6 that after injection of 111In-DTPAOC.

Internal and external tetrachloroethene exposure of persons living in differently polluted areas of Northrhine-Westphalia (Germany).

An epidemiological study was performed to measure the internal and external tetrachloroethene exposure of persons living in two differently polluted areas of Northrhine-Westphalia (Germany). Tetrachloroethene concentrations were determined in venous blood samples of 5- to 7-year-old children (n = 81) and 55-year-old women (n = 91) living in Essen, an industrial city located in the Ruhr area. 103 children und 131 women of the same age living in Borken, a small town north of the Ruhr area, served as reference group.

Neurobehavioral and neurophysiological outcome of chronic low-level tetrachloroethene exposure measured in neighborhoods of dry cleaning shops.

The effects of chronic low-level tetrachloroethene (TCE) exposure on functions of the central nervous system (CNS) were measured in subjects living in the neighborhood of dry cleaning shops with a mean residential time of 10.6 years. Neurobehavioral tests were performed using a German version of the NES battery.

[Exposure to mercury in the population. II. Mercury release from amalgam fillings].

Urinary levels of mercury (HgU) were measured in 93 males and females aged 18-63 years. Subjects with amalgam fillings (n = 72) had, on average, significantly higher levels of mercury in urine (mean = 0.57 microgram Hg/l and 0.

[Exposure to mercury in the population. I. Mercury concentrations in the urine of normal subjects].

The levels of mercury were determined in 24 h urine samples collected from 703 subjects (age 1-79 years) living in the Eastern part of the Ruhr area (West-Germany). The mean HgU level was 0.75 micrograms/l (range less than 0.

[Blood lead and blood cadmium concentrations in 55-66-year-old women fron different areas of Nordrhein-Westfalen--chronological trends during 1982-1988].

Blood lead levels were determined in 3098 55-66 year-old women living in different areas of Northrhine-Westphalia (F.R.G.

[Exposure of children to benzene and other motor vehicle emissions].

The concentrations of benzene, toluene, and lead and the percentage of carboxyhemoglobin (COHb) were measured in the venous blood of 48 children living in a central urban area with high traffic density (Cologne, FRG). The same parameters were also evaluated in a reference group of children (n = 72) living in a small city located in a rural area of West-Germany (Borken, Münsterland). The above named parameters could be quantitated in all blood samples.

Exposure to lead and cadmium of children living in different areas of north-west Germany: results of biological monitoring studies 1982-1986.

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.

Cadmium in kidney cortex of inhabitants of North-West Germany: its relationship to age, sex, smoking and environmental pollution by cadmium.

The cadmium concentration in kidney cortex (CdKc) was determined in 388 deceased persons, who at the time of death had lived in the cities of Düsseldorf and Duisburg, Federal Republic of Germany (FRG), and surrounding areas. The average CdKc concentration was found to be 17.1 micrograms/g wet weight.

Environmental exposure to cadmium and renal function of elderly women living in cadmium-polluted areas of the Federal Republic of Germany.

An epidemiological study was performed to assess whether environmental pollution by cadmium as found in cadmium-polluted areas of the Federal Republic of Germany is associated with an increased prevalence of biological signs of kidney dysfunction in population groups non-occupationally exposed to heavy metals. The study was run in two industrial areas known to be highly contaminated by cadmium, lead and other heavy metals, viz. Stolberg and Duisburg.