[The current status of chemo- or immunotherapy of gastrointestinal tumors].
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Biomedical subjects
Publications and source records attributed to M Schmidt.
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During the treatment of a manic depressive patient, the authors reported some lithium toxicity signs, as lithium carbonate (3 X 300 mg p.d.) and phenylbutazone suppository (3 X 250 mg/p.d.) were associated, this last medication being prescribed for a phlebitis. Lithiemia increased from .70 to 1,44 mEq/l., the lithiemia clearance falling from 10 ml to 5 ml/mn/1.73 m2) and the lithium tubular reabsorption percentage increasing from 85 to 94% (standard rates: 77.4 +/- 1.3%). In a second time, a rat experimentation corroborated these findings: phenylbutazone treatment (100 mg/kg/p.o. for five days) resulted in a lithium tubular reabsorption increase. It seems that the association of lithium carbonate with phenylbutazone should be avoided. The authors point out the risk of prescribing lithium and pyrazolic by-products as phenylbutazone, which are potentially nephrotoxic.
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49 patients with disseminated bronchogenic carcinoma (small cell, 16;squamous cell, 17;large cell, 12;adeno, 4) were treated with a combination of adriamycin, cyclophosphamide, vincristine and DTIC. In a randomized series (21 patients) chemotherapy alone was compared to chemotherapy plus heparin. Partial remission was achieved in 8 patients with small cell carcinoma, in 5 patients with large carcinoma and in 2 patients with squamous cell carcinoma. The survival of patients who responded to therapy was greater than the survival of patients who did not respond to therapy. The duration of remission and the survival time was not longer in patients who had additional heparin therapy.
A decrease in fibrin stabilizing factor (Factor XIII) is the most frequent coagulation disorder seen in adults with acute leukemia. Patients with prominent reduction of factor XIII (FSF) (less than 50%) were substituted with a factor XIII concentrate from human placenta, and factor XIII plasma concentration and bleeding tendency were followed up during the course of the disease. After substitution plasma, factor XIII activity went up to normal levels in most of the patients. As compared to the course of 12 patients with distinct factor XIII reduction without factor XIII therapy, there were less bleeding complications in 13 courses of patients with prominent reduction of factor XIII substituted with factor XIII concentrate and in 11 with normal or only slightly reduced factor XIII levels.
A rapid method for quantitative determination of concentration of urobilinoids of fresh urine was developed. The method is based upon extraction of urinary urobilinoids using a mixture of acetic acid and ether and followed by the extraction of the ethereal phase with Ehrlich reagent and a solution of sodium acetate. Readings of absorbance from the absorption band of reaction products from urobilinoids and Ehrlich reagent are done. Performance of the rapid method: 2 ml urine + 10 ml ether + 2 ml acetic acid were thoroughly mixed for about 15 seconds. The ethereal extract was shaken after addition of 12 ml Ehrlich-reagent for 1 minute and 15 ml half-saturated sodium acetate solution were added. 0-3 minutes afterwards reading of absorption at 560 nm respectively filter Hg 578 nm. Photometer:mg/dl=29 X A578 nm, 1 cm -0,4. Spectrophotometer:mg/dl urobilinoids=13,7 X A560 nm X 1/d -0,22 (d=optical pathway). Photometrical determination of concentration of urobilinoid can also be done using table 1. Accuracy, reproducibility and specificity are fully satisfying for clinical use of the method.
A new method has been developed for clinical determination of porphobilinogen and delta-aminolevulinic acid in urine. Compared with the method of Mauzerall and Granick, being the most commonly used method for clinical application, there is an essential reduction of work and needed time. During the flow of 0.5 ml urine on a 0.7 cm x 2 cm column of macroporous cation exchange resin in H+-form porphobilinogen and delta-aminolevulinic acid are bound to the resin. After rinsing the column with 3 ml N acetic acid and 1 ml H2O the bound hemprecursors were eluted with 5 ml buffer. Concentration of porphobilinogen and of the pyrrol, synthesized from delta-aminolevulinic acid by Knorr-reaction is measured photometrically at 546 nm after Ehrich-reaction. After a short-time regeneration of columns -- 5 ml buffer, 3 ml N acetic acid -- these columns can be reused at least 20 times.
The authors determined by means of square-wave polarography the copper, lead, cadmium and zinc contents in the tobacco and smoke of cigarettes (16 brands), cigars (5 brands) and pipe tobacco (3 brands) and discuss their possible actions on the human organism. A comparison of the amount of heavy metals taken up by an average smoker (at most 20 cigarettes per day) with the MAC values adopted in the GDR conveys the impression that the loading with copper, lead and zinc is unimportant, whereas, according to the findings of other authors, the loading with cadmium is but seemingly insignificant.
1. The effects of two groups of diuretics on renin secretion have been compared in dogs anaesthetized with pentobarbital. 2. Frusemide, ethacrynic acid and bumetanide cause an immediate rise in renin secretion which is not inhibited either by DL-propranolol or by a bilateral ureterovenous anastomosis which prevents salt and water loss. 3. Clopamide, metolazone and indapamide do not cause an immediate rise in renin secretion. Renin hypersecretion is induced only 1 h after intravenous injection of these diuretics. 4. Renin secretion was studied for 6 h after frusemide injection: the immediate rise was followed by a later increase in renin secretion. This later rise was inhibited by propranolol and by ureterovenous anastomosis. 5. These results allow us to distinguish between a direct renal mechanism responsible for early renin hypersecretion, which appears to be connected with the action of the diuretic on the ascending limb of Henle's loop, and an indirect mechanism responsible for late renin hypersecretion, which appears to be connected with salt and water loss.
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Porphobilinogen synthase was purified from ox liver by ammonium sulfate fractionation, heat denaturation and column chromatography (purification: 400-fold; specific activity 4.72 nkat). The molecular weight of the native enzyme obtained by thin-layer gel filtration is about 280 000. Using 8M urea in the presence of dithiothreitol as reducing agent, the molecule breaks down into 8 subunits of molecular weight 36 000 (dodecylsulfate gel electrophoresis); the preparation of aminoethylated subunit is described. According to the above-mentioned molecular weight and to the above-mentioned molecular weight and to the quantitative amino acid analysis after total hydrolysis, the following compositon of the enzymes subunit was calculated ASX23-25 Thr7 Ser23-24 Glx29-31 Pro22-23 Gly22-24 Ala36-37 Val23-26 Met7 Ile9 Leu34-35 Tyr10 Phe11-12 Lys11-12 Cys6-7 His6-8 Arg22 Trp1-2. The subunits, having two free sulfhydryl groups, therefore consists of a chain of about 306 amino acids. The Dansyl-Edman procedure did not enable identification of any free N-terminal amino acid. The acyl group blocking the N-terminus is an acetyl group. It was identified, after hydrazinolysis of the enzyme, by means of chromatographic comparison with 1-formyl-2-dansyl-hydrazine and 1-acetyl-2-dansylhydrazine, whose syntheses and UV spectra are described.
Human gastrointestinal cancer xenografts were established in the nude mouse. Grafts were accomplished with gastric adenocarcinomas, gastric leiomyosarcoma, histiocytic lymphoma of the stomach and gallbladder, pancreatic tumors, colonic cancers and cell lines of duodenal (HUTU-80) and pancreatic (HS-766-T) cancers, melanoma (SK-Mel-5), and murine metastasizing Lewis lung carcinoma. The rate of successful xenografting of these tumors varied from virtually 100% with colon and duodenal cancer, 50% for a pancreatic cancer (P-1), to only 17% for gastric adenocarcinoma. Pancreas and colon adenocarcinomas have been maintained by successive xenotransplantation over 16 and 19 months, respectively. Human xenografts retained morphological identity with tissues of origin through several transplant generations and shared some of their ultrastructural characteristics but did not metastasize. Rodent xenografts, of heterogenous origin were characterized by differences in the duration of the latent period and in the rate of their initial development as described by the average doubling times and average slopes (B) of their growth curves. Differences between B of the Lewis lung carcinoma and all of the human xenografts and between B of a pancreatic adenocarcinoma and three other neoplasms were significant (P less than 0.05 to 0.04). Labeling indices determined for 14 cancer transplants were in the range of previously reported data for similar neoplasms in patients or other xenograft systems. These findings suggest that the nude mouse model can be used to evaluate endogenous properties of gastrointestinal cancers and their responses to exogenous agents.
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The metabolism and in vivo kinetics of fibrinogen labelled with radioactive iodine was studied in children with cyanotic congenital heart disease. The patients had a significantly lowered plasma fibrinogen pool, shortened fibrinogen half-life and increased fractional catabolic rate of fibrinogen compared with healthy children. The average plasma fibrinogen and absolute catabolic rate of fibrinogen did not differ from control values. The shortened fibrinogen half-life together with the correcting effect of anticoagulation with heparin indicated that fibrinogen was consumed by chronic disseminated intravascular coagulation. Inhibition of the fibrinolytic system with epsilon-aminocaproic acid in three cyanotic patients had no influence on the fibrinogen half-life in two of them but resulted in its prolongation in one patient.
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