Biomedical subjects
Publications and source records attributed to R Nagel.
Azathioprine is a direct acting mutagen in Salmonella typhimurium TA100 and TA1535. Addition of rat liver S9 fraction with or without co-factors, or glutathione, causes a decrease in the mutagenicity of azathioprine in TA100 and an increase in TA1535, indicating the effect of SH groups.
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The kidneys in 15 patients (8 renal tumours, 4 cysts and 7 normal patients) were examined by means of super-conductive NMR tomography in order to assess the value of the method and its use in tumour staging. The findings were compared with computed tomography, angiography and surgery. Parenchymal tumours and cysts are easily recognised and differentiated, as they are on CT. NMR demonstrates a pseudo-capsule, which can otherwise only be seen on the angiogram, or on angio-CT. The extent in the peri- and pararenal space, infiltration into neighbouring organs and lymph nodes are equally well seen on NMR and CT. NMR equals angiography for demonstrating invasion into the renal vein and vena cava and, in this respect, is better than CT.
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Twenty-one of 32 patients with locally advanced prostatic cancer (stage C) were treated with the LH-RH analogue Buserelin for 7-19 months. After an initial sequence of subcutaneous injections, treatment was continued with intranasal spray application (three daily doses of 400 micrograms each) which ensured maintenance of serum testosterone within the range seen in castrated men. To evaluate the response of the primary tumor to Buserelin, cytological regression was established for all patients by fine-needle aspiration biopsy every 3 months. The cytological results corresponded with those of DNA analyses of single-cell cytophotometry showing a statistically significant drop of the grade of aneuploidy or polyploidy when the prostatic carcinoma responded positively to Buserelin therapy. Seventeen of 21 patients treated with the potent LH-RH analogue showed good therapy response. Four patients with no cytological signs of tumor regression received secondary treatment with estramustine phosphate because of hormone resistence. One patient had to be crossed over to cyclophosphamide, the third drug, for clinical progression after 15 months. Essential side effects have not been observed. Continuous treatment of locally advanced prostatic cancer with Buserelin, combined with close control of the patient, offers not only a real alternative to surgical castration--as the patient is spared the psychical stress of orchiectomy--but also to estrogen therapy with its risk of cardiovascular side effects.
1. Metabolism of phenol in goldfish yielded the known phenyl conjugates in fish--phenyl sulphate and phenyl glucuronide. Additionally, quinol sulphate, a new conjugate of phenol in fish, was detected.
1. The metabolism of phenol in goldfish (Carassius auratus), rainbow trout (Salmo gairdneri) and goldenorfe ide (Leuciscus ideus melanotus) was compared. All three species produced phenyl sulphate, quinol sulphate and phenyl glucuronide. 2. The dose dependence of metabolism of phenol in goldfish was investigated. When the concn. of phenol was increased from 0.2 to 2 mg/l medium, that glucuronylated increased from 7 to 16% and that sulphated decreased from 63 to 47%. 3. The influence of mode of exposure on metabolism of phenol in goldfish was examined. Dietary exposure and uptake from medium was compared with i.p. injection. There was less metabolism in the order: dietary exposure greater than uptake from medium greater than injection.
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Based on the pertinent literature, this paper discusses the results of cytostatic therapy for advanced prostatic cancer published so far with special consideration given to the extensive experience of the National Prostatic Cancer Project (NPCP) in the United States. Endoxan and 5-Fluoro-uracil, each as a monotherapy, haven proven still to be the optimal cytostatic therapies in secondary treatment following hormone resistance. Moreover, our own results reached with 33 patients on chemotherapy with Endoxan or 5-Fluoro-uracil, resp., are reported, in particular those in 24 of the 33 patients receiving these drugs as a third therapy after previous hormone resistance and secondary Estracyt resistance. Especially with regard to pain relief, we obtained good results in 50% of cases. The average survival period of the patients on third therapy was 6.7 months. Side effects prevailed in the gastrointestinal tract and the hemopoetic system. The results with Endoxan and 5-Fluoro-uracil as primary therapies have thus far been unsatisfactory with regard to therapy response and drug tolerance.
From a series of 39 patients presenting with a locally advanced cancer of the prostate (Stage C), 26 were treated with an LH-RH analogue, Buserelin, for a period ranging between 7 and 22 months. After an initial period of subcutaneous injections, the treatment was administered by intranasal spray (400 mcg three times a day). This resulted in levels of testosterone similar to those of castrated men. In order to evaluate the effects of buserelin on the primary tumour, a degree of cytological regression was established for all of the patients, using fine-needle aspiration biopsy which was performed every three months. The cytological results correspond with the DNA analyses performed by cytophotometry of isolated cells and reveal a statistically significant reduction in the degree of anaploidy or polyploidy in the cases in which the prostatic cancer had responded favourably to treatment with buserelin. 21 of the 26 patients treated with this potent LH-RH analogue showed a good therapeutic response. 5 patients who did not show any signs of cytological regression were secondarily treated with estramustine phosphate because of their resistance to hormones. One patient received cyclophosphamide as a tertiary treatment because of progression of his symptoms after 15 months. No appreciable side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
600 aspiration biopsies were performed under 6 different therapeutic conditions (estrogens, antiandrogen, Estracyt, irradiation, irradiation and estrogens, cytostatics) in patients mostly in stage T3 Nx Mo. The most important signs of regression were found in the nucleus. Compared to 102 simultaneous transrectal punch biopsies we found a diagnostic reliability for cytology of 97%. A detailed classification of the cytological signs of regression permitted a cytological grading of regression into 6 different regression grades. A surprisingly good correlation was found between grading of regression and clinical response or progression. Cytology was superior to rectal examination as a method of evaluating the effectiveness of therapies. The incidence of complications of aspiration biopsy was 1.6% and the incidence of insufficient cell material was 5.2%.
Based on 67 specimens from 20 conservatively treated undifferentiated prostate cancer patients cell nucleic acid analysis combined with a prospective clinical study was attempted using single cell scanning-cytophotometry. Regardless of therapy type a statistically significant difference in nuclear DNA-content was evident between successfully treated prostate cancers and therapy-resistant cancers. Good prognosis was suggested by a significant decline from aneuploid or polyploid to diploid nuclear-DNA-content with a narrow peak in 2c, especially within the first 12 weeks of treatment. Lack of DNA-content alteration or a DNA-frequency distribution change to the right were correlated with rapid clinical regression. Although all had undifferentiated prostate cancer morphology statistically significant differences in nuclear DNA-content were found. The prognostic value of this remains unknown.
In addition to surveying biochemistry, clinical findings and side effects of Estramustin Phosphate therapy, this paper gives an account of our own results with primary and secondary Estramustin Phosphate therapy. A total number of 118 patients have been examined in three different studies since 1970. Apart from conventional clinical control examinations, an additional accurate parameter applied to control therapy response was cytological analysis of therapy induced regression signs in primary tumor. Thus objective therapy response was established for 87% resp. 93% of the patients on primary Estramustin Phosphate therapy, and for 35% resp. 45% of those on secondary therapy. Patients with cytologically poor therapy response 3 months after beginning of therapy entered significantly earlier into clinical progression than patients with favorable therapy response, with clinical progression being additionally and essentially influenced by the pretherapeutical metastatic stage. Gastro-intestinal side-effects were prevalent in 79% of cases on intravenous administration of the drug, while on oral administration they were found to be three times less.
Nine patients with advanced carcinoma of the prostate were treated with the luteinising-hormone-releasing-hormone agonist buserelin (2 mg/day subcutaneously for 3 days then 0.4-1.2 mg/day intranasally for up to 24 weeks). There was a rise in luteinising-hormone levels during the first few days of treatment, but levels fell after 3 weeks and remained lower than normal after 24 weeks' treatment. In patients receiving 0.6-1.2 mg buserelin per day testosterone levels fell to less than 1 ng/ml within 3 weeks and were still as low as those found in surgically castrated men after 24 weeks. Histology showed regressive changes in some tumours after 3-6 months' buserelin treatment similar to those seen in surgically castrated men. Buserelin treatment may be an alternative to surgery in patients with advanced carcinoma of the prostate.
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181 of 2,606 patients hospitalized for urolithiasis in 12 years were younger than 15 years (6.9%). In accordance with the data given by other authors, we found the incidence of urolithiasis in children to be 1-5%, which, at least in Central Europe, corresponds approximately with that in adults. The causative factors or cofactors we established were malformation of the kidneys and urinary tract in 35.9%, and infections of the urinary tract in 80.7%. Defined metabolic disorders were found in only 5.5% of patients. Stone analysis showed a predominance of phosphate-containing calculi. Control examinations were done in 154 children over periods of 6 months to 11 years. "Recurrent lithiasis' was seen in 32 patients, however, the exact comparison of pre- and postoperative X-ray films showed that in 17 cases the calculi had not been completely removed during surgery (11%). Consequently, a real recurrent lithiasis was present in 15 children only (9.9%). Since the West Berlin population includes a high percentage of Turkish people, we can conclude from our case material that even those Turkish children who were born in West Berlin suffer from urolithiasis 2-2.5 times as often as German children of the same age-groups.
On 138 patients with radiologic filling defects in the ureter and renal pelvis lavage cytology was done. With this method it was possible to recognize clearly 39 of 47 urothelial tumors of renal pelvis and ureter (81,3%). Lavage cytology failed in patients with hypernephroma. Severe cellular atypias could be seen in patients with urolithiasis and inflammation. The diagnostic reliability of lavage cytology with urothelial tumors of renal pelvis and ureter is far greater than that of exfoliative urinary cytology and reaches results as good as those from brush biopsy.