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Biomedical subjects

K Wegener

Publications and source records attributed to K Wegener.

At least 37 records · Page 2Linked to original sources

The effects of Thorotrast and quartz on the induction of lung tumors in rats.

In a long-term animal study, the combined and separate effects of Thorotrast (colloidal 232ThO2) and silica dust on the induction of lung tumors were investigated. Female Wistar rats were exposed for 29 d to aerosol concentrations of quartz of either 6 mg m-3, 30 mg m-3, or 0 mg m-3 (6 h d-1, 5 d wk-1). After inhalation, one-half of all exposed animals received a single intravenous injection of enriched Thorotrast (600 microL, 2960 Bq 228 Th mL-1). In all quartz-exposed groups the incidence of benign and malignant lung tumors turned out to be more than 40%. The additional Thorotrast treatment (lifelong exhalation of 220Rn) led to a marked shortening of latency times (first lung tumor was found 1 y after treatment) and to a higher total incidence in the animals exposed to 30 mg m-3 quartz (57 of 87 animals with lung tumors = 65.5%). In the group treated only with Thorotrast, three of 87 animals developed lung tumors. Statistical methods that correct for intercurrent mortality showed a significant increase of the lung tumor risk with respect to Thorotrast treatment, even for the low quartz groups with nearly similar incidences of lung tumors (in the group with ThO2, 39 out of 87 = 44.8%; in the group without ThO2, 37 out of 82 = 45.1%). The tumors were found predominantly in the peripheral regions of the lung and were preceded by proliferation and hyperplasia of the alveolar and bronchiolar epithelium. The results demonstrate a pronounced interactive effect of quartz and Thorotrast on carcinogenesis of the lung. The underlying possible mechanisms are discussed.

Adenocarcinoma, Bronchiolo-Alveolar↗

The combined and separate action of neutron radiation and zirconium dioxide on the liver of rats.

To simulate the chronic alpha radiation of Thorotrast, the liver of female Wistar rats was exposed to fractionated neutron irradiation at 14-d intervals (0.2 Gy per fraction) over 2 y to a total dose of 10.0 Gy. Prior to the start of irradiation, one-half of the animals received 120 microL of non-radioactive Zirconotrast (ZrO2), which is comparable to Thorotrast with regard to all other physical and chemical properties. One year after beginning irradiation, the first liver tumor was detected. At the end of the life-span study, the incidence of irradiated animals with liver tumors was about 40%. In the animals treated additionally with ZrO2, the incidence, time of onset, and overall number of liver tumors was nearly equal, indicating that the fractionated neutron irradiation was the exclusive cause of tumor development. The lifelong-deposited ZrO2 colloid had no stimulating effect. Compared to earlier animal studies dealing with Thorotrast, the same histological types of benign and malignant liver tumors were found.

Adenoma, Bile Duct↗

[The significance of papillary biopsy in obstruction of Vater's papilla].

Biopsies of the papilla of Vater were taken in 53 patients after a papillotomy had been carried out during a previous ERC. The macroscopic finding of a papillary stenosis of unknown dignity required an exact histological diagnosis. In 35 patients (66%) a duodenitis/papillitis was found on the histological specimens, in 6 patients (11%) a villous adenoma, and in 7 patients an adenocarcinoma (13%). A metastasis of a melanoma, a schwannoma, and a coagulum were diagnosed once. The papillotomy preceding the biopsy was the only necessary therapy in 46 patients, and endoprosthesis was inserted in 5 patients. In 2 patients the tumor was excised by snare, in 4 patients a surgical resection was carried out. The incidence of malignancy in papillary stenosis emphasizes the significance of a biopsy for histological confirmation of the diagnosis if endoscopically a papillary stenosis is detected.

Adenocarcinoma↗

[Polyposis of the stomach caused by multiple xanthomas].

Case report on a rare gastric polyposis. Endoscopically the lesions appear as multiple, yellowish, partly villous polypoid changes histologically representing as foam cells und showing deposits of lipids on characteristic stains. Etiopathogenesis are these lesions and their differential diagnosis are discussed.

Diagnosis, Differential↗

[Malignant melanoma of the nailbed under a skin graft].

The authors report on a case of subungual malignant melanoma, which developed beneath a split-skin graft. The patient had an accident which caused a pathologic growth of the nail. Eleven years later the patient removed the nail, because it became moist, and a surgeon grafted the nail-bed with a split-thickness skin. Six years later we saw a 2 X 2 cm tumor under the skin graft and histologic examination showed a nodular malignant melanoma. Diagnostic and therapeutic guidelines for subungual and acral melanomas are discussed.

Diagnosis, Differential↗

Recent results of the German Thorotrast study--epidemiological results and dose effect relationships in Thorotrast patients.

The German Thorotrast Study includes 5159 Thorotrast patients and 5160 control patients. 887 Thorotrast patients and 660 control patients could be clinically and biophysically examined and followed-up. The mean age at injection or hospitalization in the case of the control group was 28 yr. The mean injected volume of Thorotrast was calculated to be 24.7 ml and the X-ray films of 249 Thorotrast patients showed paravascular deposits. In the meantime 432 Thorotrast patients and 122 patients of the control group have died. Among the deceased patients we have registered (Thorotrast vs control): hepatic tumors 152/0; myeloproliferative diseases 10/0; Hodgkin's diseases 2/0; non-Hodgkin's lymphomas 5/1; bronchogenic carcinomas 13/6; pleural mesothelioma 1/0; bone sarcoma 1/1(?); sarcoma at injection site 1/0; hepatic cirrhosis 90/6; bone marrow failure 8/1; other neoplastic diseases 46/19; other non-neoplastic diseases 151/88. The cumulative incidence of liver tumors depends on the dose rate to liver tissue and is not influenced by the age at injection. A dose effect relationship for the myeloproliferative diseases is not yet apparent.

Adolescent↗

Recent results of the German Thorotrast study--pathoanatomical changes in animal experiments and comparison to human thorotrastosis.

A survival experiment is described in which 1920 Wistar rats were used. These rats were injected intravenously with different quantities and different alpha-doses of Thorotrast. The following observations were made: The distribution of Thorotrast in the liver of the experimental animals is similar to that in human livers. Liver fibrosis and liver cirrhosis are rarely seen in experimental animals. The liver cell carcinomas, intrahepatic bile duct carcinomas and haemangiosarcomas that developed in the liver of the rats showed an identical biology and morphology with those seen in corresponding Thorotrast tumours in human patients. One particular tumour type that occurred in the liver of the rats probably represents a Kupffer cell sarcoma: the tumour cells show a positive peroxidase reaction and the metastases contained Thorotrast. Unlike human Thorotrast liver tumours, rat liver tumours include benign tumours such as liver cell adenomas and intrahepatic bile duct adenomas. The animals of the control group did not develop these benign liver tumours. The total frequency of the liver and spleen tumours in the trial groups receiving 230Th enriched Thorotrast was dependent on the dose given. The relationship between dose and effect was almost linear. The volume of the injected Thorotrast quantity, given a constant dose rate, seems to have only a slight influence on the number of tumours.

Animals↗

Recent results of the German Thorotrast study--statistical evaluation of animal experiments with regard to the nonradiation effects in human thorotrastosis.

Our first long-term animal experiment made use of 1920 female Wistar rats divided into 20 groups of 96 animals each. These were injected at 12 weeks of age with different volumes and different dosages of Thorotrast which was enriched with 230Th to enhance the alpha-energy emission rate. The purpose of the study was to evaluate the effects due to the colloidal substance and the radiation. In the main experiment, 12 groups of rats were injected intravenously with 60, 120 and 300 microliters Thorotrast. 230Th was added to some Thorotrast preparations so that the total alpha-energy emission rate varied by factors of 1, 2, 5 and 10 relative to normal Thorotrast. Two groups were injected with 12 and 60 microliters of 50-fold enriched Thorotrast. One group was given 600 microliters of normal Thorotrast. In addition, we had 5 control groups, 1 NaCl and 4 Dextrin groups. The latter were injected with 60, 120, 300 or 600 microliters of Dextrin. The first animals died 8 months after injection, and the last 11 animals were killed 41 months after starting the experiment. The number of animals that developed a hepatic or splenic tumor increased by a factor of 10 in the highest dose-rate groups compared to controls. Our results demonstrated a linear correlation between the dose-rate and the number of primary hepatic and splenic tumors. It appeared that the volume of injected Thorotrast, by itself, had little influence on the number of tumors. However, at a constant dose-rate of 10, a 50-fold increase in the volume of Thorotrast (12-600 microliters) decreased the minimal tumor-appearance time by about 250 days.

Animals↗

Comparison of the toxins of the blue-green alga Aphanizomenon flos-aquae with the Gonyaulax toxins.

A toxic strain of Aphanizomenon flos-aquae (NH-1), isolated from a toxic bloom in a pond in Durham, New Hampshire, has been mass cultured in the laboratory. The toxin was extracted by ultrasonic disruption of the cells and purified by; (a) filtration through a 10 kilodalton filter, and (b) chromatography on a strong cation exchange resin column using 0.01 M, then 0.1 M, pH 5, sodium acetate buffer followed by 0.75 M hydrochloric acid. Mouse assays and fluorescence generated by hydrogen peroxide oxidation were used to monitor the fractions. Only a nonfluorescent toxic peak followed immediately by a fluorescent less-toxic peak were detected, both eluting with the hydrochloric acid fractions. The toxins were identical in behavior to neosaxitoxin and saxitoxin, respectively, when compared with elution profiles of the paralytic shellfish poisons from Gonyaulax tamarensis var. excavata and by paper electrophoretic and thin-layer chromatographic comparisons. The toxin profile appears to be different from that of a previously isolated strain of A. flos-aquae from Kezar Lake.

Animals↗

Double tumours of the liver following intravenous thorotrast injection. Patho-anatomical report on two cases.

Observations on the contrast between the livers of two patients who underwent an arteriogram with thorotrast in 1941 have been made. The first case produced a cholangicellular carcinoma (CCC) in addition to atypical proliferations of sinusoidal lining cells. The second case produced a very rare tumour combination of a CCC with a haemangioendothelial sarcoma (Haem-SA the problem of double tumours of the liver following thorotrast injection is discussed in the light of these cases. In addition the discussion includes various opinions on Kupffer cells.

Adenoma, Bile Duct↗