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Several authors reported about acute haemodynamic effects of ADM years ago. We studied this problem in five patients in the invasive and noninvasive way and thus obtained the most important haemodynamic parameters. Acute haemodynamic effects in the meaning of a negative inotropy and vasodilatation are confirmed. The usual intravenous injection does not avoid the decrease of important haemodynamic parameters (SV, SWI, CI) even though injected over ten minutes. Possible infarction and complications during the injection may be the result of decrease of perfusion pressure in the meaning of a "steal phenomenon".

Surface phenotypes of lymphocytes and the assessment of cytotoxic NK activity were determined in peripheral blood leukocytes in a group of heavy smokers and respective non-smoking people control group. Cell phenotypes were evaluated by a panel of monoclonal antibodies by indirect immunofluorescence on cell sediments. Cytotoxic activity was assessed by single cell cytotoxic assay on target K 562 cells. There were no significant differences in T cell (CD 3+) as well as in CD 43+ ones (large sialoglycoprotein) per cent values. The cells possessing receptor for sheep red blood cell (CD 2+) were however more numerous in smokers as compared to non-smokers. Per cent value of B lymphocytes in the former group was significantly decreased vs control one. There was no difference in per cent values of activated and immature cells in both examined groups. Per cent values of NK cell activity were higher in non-smokers in relation to smokers. It was reflected by an increase of cytotoxicity of effector cells, while frequency of incidence of NK cells was comparable in both groups examined.

The pre- and postnatal administration of DEMNU induces a high frequency of tumors when applied via the intravenous route, and the latency periods show a dose dependence (table I). Tumors of the brain, spinal cord and cranial nerves clearly predominate. Furthermore, a large number of neoplasms of kidney, heart and soft tissue was observed (table II). As DEMNU is per se a very stable compound, it is suggested that this agent is metabolized by monooxygenases. 3-Ethyl-1-methyl-1-nitrosourea should be formed as an intermediate product via this pathway, which is relatively stable and might explain the mainly neurotropic carcinogenicity of DEMNU. Species differences in the carcinogenicity of trialkyl-nitrosoureas and the mode of metabolic activation are discussed.

Cancer incidence rates in Turkey are compared to those in two regions of West Germany, namely Hamburg and Saarland. Incidence rates of laryngeal, colorectal and prostatic cancer are significantly different in males of the two countries. Additionally, incidence rates of skin and trachea, bronchus, lung cancer show statistically significant differences in males of Turkey and Saarland. Between females, only the incidence of colorectal cancer is significantly different in both countries. These variations in cancer occurrence may be due to differences in tobacco and alcohol consumption, age distribution of the two populations and exposure to sunlight.

In an experimental murine metastasis model host pretreatment protocol (HPP) was tested to abrogate lung colonization of tumor cells. The stimulation of the host defense by lentinan or TP4, and the PGI2 administration was effective in the case of the immunosensitive low metastatic tumor. The modulation of the host cells and/or the extracellular matrix by the glycosaminoglycan biosynthesis blocking agent KL-103--but not by the degradation inhibitor suramin--inhibited the lung colonization of the highly metastatic immunoresistant tumor variant. In combination with the cytotoxic antiproliferative agents these non-toxic drugs could be useful in new protocols to prevent tumor dissemination.

Evidence supporting a role of mycotoxin, in particular ochratoxin A (OA) and citrinin, in the etiology of Balkan endemic nephropathy (BEN) and associated urinary tract tumours (UTT) is reviewed. Both diseases occur in subjects born and/or living in certain rural areas where home-produced and home-stored stable foods were found to be more frequently contaminated by the OA and citrinin. OA levels in blood and urine from patients with BEN or UTT were higher than in controls. OA and possibly other mycotoxins cause endemic porcine nephropathy, a disease with morphology and clinical course similar to those of BEN. OA was carcinogenic in two rodent species with kidney as a major target organ. Animals and strains phenotype as fast metabolizers of debrisoquine were more susceptible to OA-induced carcinogenicity. Among BEN/UTT patients, a greater proportion of fast metabolizers was reported. Although no epidemiological proof of a direct causal role of mycotoxins in BEN/UTT etiology has been presented, the data accumulated so far indicate a need for prospective studies in which mycotoxins as well as other risk factors should be considered.

Graffi et al. (1-3) had proposed the use of exogenous enzymes to toxify inactive transport forms of cancerostatic substances. For this purpose, the pH difference between normal tissues and the tumor was to be exploited, which can be essentially increased by the application of glucose and inorganic phosphate (5-7). Earlier studies using alpha-L-arabinofuranosidase obtained from Aspergillus niger have shown that the selectivity of tumor chemotherapy can be increased in this way (4). The alpha-L-arabinofuranosidases known to date are stabile in a wide pH range (9). However, in some moulds we found pH-labile enzymes of this kind that become irreversibly inactivated in the weakly alkaline or neutral pH range (10, 11). Studies on the distribution of the activity of a pH-labile alpha-L-arabinofuranosidase from Glomerella myabana in tumor-bearing mice have shown that this enzyme is rapidly eliminated from the organism, in contrast to the pH-stable alpha-L-arabinofuranosidase from A. niger. Apart from its excretion via kidney and liver, of importance is the inactivation of the enzyme in the normal tissues. The additional application of glucose strongly increased the activity of this enzyme both in the tumor and in normal tissues (12). By injecting alkaline solutions, stronger inactivation in normal tissues than in the tumor was achieved (13). In the present paper, distribution of an alpha-L-arabinofuranosidase from Fusarium species I 50 (11), inactive already at pH 7.0 (37 degrees C), was studied in tumor-bearing mice. The activity of this enzyme could be enriched under various conditions in the tumor, and especially favorable proved to be the additional application of a combination of glucose and inorganic phosphate. Under these conditions, a higher activity than in the tumor was demonstrable only in the kidney, which can possibly be eliminated in larger experimental animals by diuretics or an appropriate alkaline administration. The investigations have shown that the pH-labile alpha-L-arabinofuranosidases, especially those of Fusarium sp., due to their pharmacokinetic behavior are better suited for use in our therapy concept than the hitherto employed enzyme from A. niger. More recently, Tietze (16) has proposed a similar therapy concept, in which also the glucose-increased pH difference between tumor and normal tissue using tumor-own enzymes, exogenous enzymes as well as transport forms of cancerostatic agents spontaneously hydrolysing under weakly acidic pH conditions is to be exploited.

The laser-induced fluorescence of hematoporphyrin derivative (HpD) sensitized experimental Ehrlich carcinoma on mice is investigated. The fluorescence is excited with the 364-nm argon laser line. The tumor fluorescence spectra are recorded in the red spectral region. The HpD induced fluorescence of the tumors is superimposed on the autofluorescence of tissue. The tumor fluorescence shows a maximum 4 h after i.p. application of HpD. The fluorescence intensity is reduced by strong excitation causing bleaching of the HpD absorption. The fluorescence spectrum is also changing and the generation of a fluorescent photoproduct is observed.

At present, the influence of BSE on mortality reduction from breast cancer is not yet clear. Within a larger case-control study in 195 cases and 390 controls, BSE practice, factors influencing BSE-frequency and the impact of BSE on tumor size as well as on the number of positive lymph-nodes have been investigated. 44% of women practised BSE monthly. Factors significantly positively correlated with BSE were older age, higher education, prior breast biopsy, participation in cervical cancer screening and regular physical breast examination. In comparison to non-users, BSE users had a relative risk for breast cancer more than 3 cm in tumor size of 0.65 (0.35-1.21). The relative risk of BSE-users for breast cancer with more than 3 positive lymph-nodes at the time of diagnosis amounted to 0.62 (0.33-1.18).