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Biomedical subjects

H Wesch

Publications and source records attributed to H Wesch.

At least 37 records · Page 2Linked to original sources

Human papillomavirus DNA in women without and with cytological abnormalities: results of a 5-year follow-up study.

To determine the prevalence of HPV 6, 11, 16, and 18 in a population without cytological or histological abnormalities, the cervical smears of women attending three clinics in Germany were screened over the past 5 years. The filter in situ hybridization method was used throughout. A total of 20,161 smears, taken from 11,667 women, were tested. When the results of only the first examination are considered, 8.8% (950/10,778) of women with normal cytology were positive for HPV DNA. If we divide the latter into age groups, 11% (852 HPV positive/7716) were below the age of 55 years and 3.2% (98 HPV positive/3062) were above this age. When the samples from patients who had undergone at least two examinations and remained cytologically negative during the 5-year period were examined (total, 2709 women), the HPV DNA positively increased to 34.7% (640/1862) for the sexually active age groups and to 9.0% (76/847) for those above 55 years of age. This study reveals that, although papillomaviral production is most pronounced in younger women, these infections are quite common in all age groups. During the period of investigation, 19 (0.65%) patients, who were diagnosed as cytologically negative at the first examination, progressed to carcinoma in situ or invasive carcinoma. Of these, 63.2% revealed a detectable HPV infection during the study period. The progression of HPV-positive women from normal cytology to CIN or cancer occurred at an annual frequency of 0.082%. With an infected lifespan of 45 years assumed, this results in a lifetime risk of 3.7%.

Adolescent↗

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↗

Neoplastic diseases induced by chronic alpha-irradiation--epidemiological, biophysical and clinical results of the German Thorotrast Study.

The intravascular injection of the formerly used contrast medium Thorotrast--a colloidal suspension of thorium-dioxide--causes a chronic exposure to alpha-particles especially in the organs of the reticuloendothelial system. The German Thorotrast Study comprises 2326 Thorotrast patients and 1890 contemporary matched patients in the control group to be evaluated. 899 Thorotrast patients and 662 controls had clinical and biophysical follow-up examinations every two years since 1969. The recent most important results of the study are: A high excess rate of primary liver cancer (410/2) was observed beginning after the 15th year of exposure. 31% of the tumors are combined with cirrhosis and 6% with other neoplastic diseases. A clear (mean) dose rate effect relationship exists. The tumor frequency depends on the time of exposure or the cumulative dose to the liver respectively and not primarily on the age at injection. The lowest cumulative doses at 10 years before diagnosis of liver cancer were about 2 Gy. Risk estimates for liver cancer after 40 years of exposure are 500 malignant tumors per 10(4) person-Gy for men and 300 for women. A high excess rate exists also for leukaemias (excluding CLL) starting already 5 years after Thorotrast injection (39/4). The lowest cumulative doses to the red bone marrow at time of death were about 0.5 Gy. According to the present result, an excess rate can be expected for carcinomas of the extrahepatic bile ducts, pancreas, oesophagus, larynx, as well as Non-Hodgkin's lymphomas, bone sarcomas, plasmacytomas and mesotheliomas.

Adolescent↗

Human papillomavirus infections in women with and without abnormal cervical cytology.

9295 smears, obtained from women attending three gynaecological hospitals for routine screening, were examined for human papillomavirus (HPV) types 6 and 11 and HPV 16 and 18 infections by filter in-situ hybridisation. The data were compared with cytological findings. In women with normal cytological smears HPV infection was identified in about 10% of women aged between 15 and 50 years and in less than 5% of those aged over 50. In women with abnormal smears (cervical intraepithelial neoplasia [CIN] I, II, and III and invasive cancer) HPV infection was detected in 35-40%; this rate seemed to be age-independent. the Peak incidence of CIN appeared several years after that of HPV infection. In women aged greater than 30 years it also declined earlier than did HPV positivity. The age-group distribution of women with CIN I, II, and III differed significantly from that of patients with invasive cancer. Only about a third of HPV-positive patients remained virus-positive, probably because of fluctuations in virus production and the insensitivity of the test system used. It is possible that filter in-situ hybridisation underestimates the total rate of HPV infections by a factor of 2 to 3.

Adolescent↗

Localization of xanthine oxidase in crystalline cores of peroxisomes. A cytochemical and biochemical study.

The ultrastructural cytochemical localization of xanthine oxidase activity in rat liver was investigated by the cerium technique. The reaction product was found in the cytoplasm of endothelial cells in liver sinusoids and, in addition, in crystalline cores of peroxisomes of liver parenchymal cells. Xanthine oxidase was also present in peroxisomal cores of beef liver and kidney, but not in rat kidney peroxisomes, which lack crystalline cores. The localization in peroxisomal cores of rat liver was confirmed also biochemically using highly purified peroxisomal fractions and subfractions containing exclusively the crystalline cores. Moreover, high levels of molybdenum were found in isolated peroxisomal cores by atomic absorption spectroscopy, thus corroborating the association of the molybdenum-containing enzyme with the cores. Since urate oxidase is also present within the same compartment of peroxisomes, it is possible that the crystalline cores harbor a complex of several enzymes involved in the purine metabolism.

Animals↗

Comparative bone analysis via inflammation-mediated osteopenia (IMO) in the rat.

Various methods exist for determination of trabecular or total bone mass in animal experiments. There is one group of simple techniques not requiring sophisticated equipment focusing on bone-calcium determination. By contrast, another group of newer methods requires complex equipment for procedures such as computerized analysis of bone X-rays or of nondecalcified bone sections. The methods of the first group require considerable time to perform, whereas those of the second group allow a great number of analyses in a short time. We have adapted the computerized techniques to the determination of rat-bone mass and then compared both types of methodology using the new animal model for pathological loss of bone mass: the syndrome of inflammation-mediated osteopenia (IMO) in rats [1, 2]. Reliable results were obtained with both approaches, but we recommend the use of one of the new techniques in cases where a large number of analyses is required.

Absorptiometry, Photon↗

Contribution of paramagnetic trace elements to the spin-lattice relaxation time in the liver.

The relaxation times of water protons in rat liver tissue were measured with a NMR spectrometer at 20 MHz. The paramagnetic trace elements Cu, Fe, and Mn were determined by neutron activation analysis. No shortening of T1 could be observed when liver Cu or Fe concentration was increased in the microgram range. T1 was strongly correlated with the liver Mn concentration of untreated animals and animals whose liver Mn concentration was artificially increased or decreased by intravenous injection of manganous acetate or a metal chelating agent with high affinity for hepatobiliary excretion. Deviations from this Mn-T1 correlation were found in the initial phase of liver cirrhosis induced by thioacetamide (elongated T1, normal Mn concentration) and after stimulation of liver growth by phenobarbital (normal T1, decreased Mn concentration). An increased or decreased enhancement factor for Mn may have contributed to the observed deviations during phenobarbital and thioacetamide treatment.

Animals↗

[5MHz realtime sonography of the breast. 2. Examination technic and diagnostic value].

The diagnostic value of mamma-sonography using realtime technique was evaluated in a prospective study based on the experience of 452 pathomorphologically confirmed sonographic results. Large cysts (greater than 1 cm) were correctly classified as 97%, while small cysts (less than or equal to 1 cm) were recognized in 84%. Eighty-six percent of the fibroadenomas were visualized; 50% of these lesions were classified as "benign" and 34% as "equivocal--probably benign". In 70% of the patients with mastopathic alterations, no abnormalities were detected sonographically, except when cystic lesions (greater than 3 mm) were present. Fifty-percent of the in-situ-carcinomas and small carcinomas (less than or equal to 1 cm) were recognized, while 97% of the larger carcinomas (greater than 1 cm) were demonstrated. The frequency of the different echographic criteria was analyzed with regard to the pathohistological results.

Adenofibroma↗

[Renal acid excretion and renal molar load in healthy children and adults].

The urinary excretion of the quantitatively prevalent ions and nonionic solutes and of aldosterone-18-glucuronide was investigated in 49 healthy children and 22 healthy adults living at home. The median of renal net-acid-excretion was 0.99 meq/kg/day or 48 meq/day/1.73 m2 in children, and 0.75 meq/kg/day or 50 meq/day/1.73 m2 in adults. The median of osmolar load was 12.8 mosmol/kg/day or 643 mosmol/day/1.73 m2 in children, and 10.6 mosmol/kg/day or 661 mosmol/day/1.73 m2 in adults. High urinary osmolality was more frequently observed in children than in adults. The data may define a desirable range of renal net-acid-excretion (0.5-1.5 meq/kg/day) in children receiving synthetic diets.

Acid-Base Equilibrium↗

Postsurgical follow-up of colorectal cancer patients monitored by the leukocyte migration test.

Blood samples from more than 1,000 patients with colorectal cancer were tested in the leukocyte migration test (LMT) and by a radioimmunoassay for carcinoembryonic antigen (CEA) for evaluation of: 1) the correlation of LMT response to the status of disease and 2) the use of LMT and CEA determination in the monitoring of patients after surgical removal of the primary tumor. A total of 320 patients, which were tested repeatedly, constituted the key group of the investigation: Of these, 56 patients developed recurrences or metastases whereas 217 patients showed no sign of reactivated disease. The group of patients with persistent absence of disease showed test profiles of either persistent negativity (50%) or conversion of one or both parameters; persistently positive profiles were rarely encountered. Patients with recurrences and metastases showed either positive profiles or conversion of positivity; only 3 patients were negative in both tests. However, despite significant disease-related response of the LMT, the test is not recommended as an adjunct to postsurgical monitoring, because of its technical complexity.

Carcinoembryonic Antigen↗

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↗