[Significance of a new tumor marker for breast carcinoma and ovarian carcinoma].
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Biomedical subjects
Publications and source records attributed to L Hoffmann.
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Albino rats bred in the institute (Wistar line) divided into 3 groups of 9 animals each received, beginning at the age of 4 weeks, feed mixtures with 10, 40 and 70% protein in the rations over a period of 24 weeks divided into 14 subperiods of study. The feed mixture changed cyclically for the groups of animals after each sub-period. Every period was divided into a growth period (8 days) with the rats kept in metabolism cages and a period of feeding on maintenance level (4 days) with the rats kept in respiration chambers. In both periods the temperature was kept constant at 30 degrees C. On 3 days of feeding on the maintenance level the metabolism parameters of energy, C and N metabolism were measured and energy maintenance requirement was ascertained. Both the energy maintenance requirement of the growing rats (up to 200 g live weight) and that of the nearly fully grown and fully grown rats resp. (greater than 200 g live weight) significantly depended on the nutrient composition of the feed mixtures supplied. It increased with the increasing protein and simultaneously decreasing carbohydrate quotas in the feed. On an average of the studies the rats had, in the sequence of 10, 40 and 70% protein content, an energy maintenance requirement of 383 +/- 31 (n = 105), 415 +/- 31 (n = 106) and 459 +/- 36 kJ metabolizable energy/kg LW0.75.d (n = 102). Energy maintenance requirement behaved relatively like 100:108:120. Based on the fact that energy maintenance requirement may be considered the requirement of ATP, relative expectancy values for energy maintenance requirement can be calculated with the energetic efficiency of the ATP synthesis (kJ metabolizable energy/Mol ATP gain) in nutrient catabolism from the relation of the experimentally ascertained nutrient metabolism at a variant supply of protein of 100:110:118. The hypothesis that the efficiency of ATP synthesis in the catabolism of the main nutrients supplying energy can be considered a relative measure of the dependence of the energy maintenance requirement on nutrient composition has been confirmed in this experiment. Different findings in earlier experiments raise the question if those findings were influenced by adaptation effects. An experimental solution of this question is considered important.
In an experiment with broilers (origin Tetra B) and with rats (albino, Wistar line) with 2 animals each, heat production was ascertained by measuring CO2 production and O2 consumption over 20 minutes after their feeding 18 h and 1 h before the beginning of measuring at ambient temperatures of 30, 25, 20, 15 and 10 degrees C. Every variant was followed through over 6 h/d in 12 measuring sections. The feed amount/ánimal and day was adapted to energy maintenance requirement. At the beginning of the experiments the broilers and rats were 14 and 21 weeks old resp. and weighed 2.2 kg and 220 g resp. The variation of the ambient temperature did not influence the heat production of the broilers. In contrast to this, the time of feeding in relation to the beginning of measuring had a distinct effect on heat production. Whereas a heat production of 342 +/- 34 kJ/kg LW0.75.d was ascertained in the postabsorptive state 18 h after the last feed intake, it increased by 11% to 393 +/- 32 kJ/kg LW0.75.d when measuring began 1 h after feeding. The very act of feed intake increased heat production by 75%. Rats showed a distinct increase of heat production caused by a decreasing ambient temperature. In the temperature range of 30-25 degrees C the increase was shallower than in the range of 25-10 degrees C. Per 1 degrees C below 25 degrees C heat production increased by 30 kJ/kg LW0.75.d. The increase was independent of the metabolism level, which was influenced by the feeding variants. The results are discussed in connection with Rubner's theory of heat compensation.
In 2 experiments with young broiler chickens, origin Tetra B, heat production was measured in dependence on ambient temperature indirectly and with the gas exchange both over 24 h and in 20-minute periods beginning on their 5th day of live. The chickens, divided into 2 X 2 groups according to sex, were constantly kept in a climatic chamber changed in to a respiration chamber during the 8- or 11-week-long experiments. The maximum variation of the temperature was between 5 and 35 degrees C. In the periods of 24-h measurements over 4 days each, the ambient temperature was changed from day to day in steps of 5 degrees C. Heat production was influenced by the age of the chickens, energy intake and ambient temperature. The results of the measurements at the same age and the same energy intake and a temperature variation between 5 and 35 degrees C can well be described by polynomes of the 3rd degree up to the 8th week of live. The thermoregulatory conditioned heat production per 1 degree C below the critical temperature decreased with the age of the chickens. In the first few weeks of life it was 20 kJ, in the 6th and 7th weeks of life 10-15 kJ and then decreased to 4-5 kJ/kg life weight 0.75.d. degrees C. Based on the temperature of minimal heat production, the heat production of 16- to 30-day-old chickens increased to 60-80% at an ambient temperature of 5 degrees C; the metabolism of chickens older than 7 weeks was only increased by about 20%. For the first 2 weeks 35 degrees C were ascertained as critical temperature, for the 3rd to 6th weeks 30 degrees C and for the 7th and 8th weeks 25 degrees C.
In the period of 1975-1982 6 experiments with young female cattle of various rearing intensities were carried out. The respiration trial technique for the measuring of energy and protein metabolization in connection with the registration of a number of rumen physiologic data were applied together with comparative studies of the digestibility and the rumen fermentation of the rations used with young cattle and with fully grown sheep. The extent of the experiment was characterized by 695 metabolism periods in calves and young cattle as well as by 149 comparative studies of the digestibility and the rumen metabolism of the fully grown sheep. The results ascertained are the basis of the derivation of the energy requirement for the rearing of young female cattle according to factorial criteria. This first out of six papers on these experiments comprises an outline of the experiment arrangement, the material and the methods as well as of the live weight development of the animals. In four of the six experiments there was a continuous monthly registration of the measured values over the complete period of the rearing of the weaned calves up to their calving with four animals each under conditions of extremely high (experiment 1), medium (experiments 5 and 6) and low (experiment 3) rearing intensity. Experiments 2 and 4 provide additional information on rearing periods under special consideration of the gestation period. In experiment 1 the cows were not milked after the first calving, and measuring was continued to the second calving of the animals.
The second installment of information on studies over several years of the energy requirement of young female cattle comprises data of the feed intake, the digestibility and metabolizability of the rations used as well as the nitrogen and energy balances of the test animals in six experiments with varying rearing intensities, in which the N, C and energy balances as well as rumen physiologic values were measured monthly using the respiration test technique. Of four experiments, measured values are available over the whole rearing period from calf to calving. The results received from 680 interpretable test periods are-separated for the six experiments--arranged in aggregate form according to live weight range in order to characterize the development of nutrient and energy metabolization processes at various rearing intensities. The results form an essential basis for the derivation of the energy requirement of young female cattle according to factorial criteria.
In 89 preparations of patients with a carcinoma of the prostate and 100 preparations of patients with a hyperplasia of the prostate (adenoma of the neck of the bladder) the appearance of primarily atypical hyperplasias was investigated. In these cases in the carcinoma group in the uniform as well as in the pluriform carcinomas a coincidence of carcinoma and atypical hyperplasia of 55% was found. The coincidence is particularly high in adenocarcinomas and in carcinomas with dominating adenoid part, respectively, i. e. in more mature glandular structures. Among the various histological types of the atypical hyperplasia the microglandular/papillary clear-cellular form is dominating with 82%. In the group of the benign hyperplasia of the prostate gland a coincidence of the atypical hyperplasia of 33% was found. Though this rate, in comparison to other investigators, seems to be relatively high, it is still significantly lower than in the carcinoma. From this follows that the atypical hyperplasia, particularly its severest forms and dysplastic deformations from other hyperplasias (postatrophic hyperplasia, basal cell hyperplasia, atrophy and metaplasia of the prostate) now as ever are suspected that these cases in question are precancerous lesions. For the clinically working urologist the task is derived in such histopathological diagnoses by clinical and bioptical follow-up controls to find an already existing, but still unrecognized, or developing carcinoma of the prostate gland. In no case the diagnosis may cause surplus therapeutic consequences.
In a group of 44 patients with a histologically ascertained metastasizing carcinoma of the prostate gland the palliative hormone treatment with Turisteron which has been performed as routine therapy since 1982 is described. The experiences concerning the advantages of this therapy with regard to the absence of hepatotoxic side effects and the high compliance of patients, the appearance of cardiovascular complications among 39 evaluable cases are compared. A distinct reduction of these side effects is possible by an aimed cardiac therapy, prophylaxis of thrombosis and use of diuretics.
The tumor markers CA 19-9 and CA 125 defined by the monoclonal antibodies 19-9 and OC 125 were investigated with respect to organ specificity and tumor sensitivity. Normal and tumor tissue specimens, and blood samples from 34 patients with pancreatic carcinomas, 40 with ovarian carcinomas and 39 with miscellaneous tumors were examined. CA 19-9 and CA 125 were determined by immunohistochemistry (IH) applied to sections of the tumors and adjacent normal tissues. In parallel, the antigens were measured in the patients' sera by radioimmunoassay (RIA). By means of IH CA 19-9 and CA 125 were detected in normal surface cells from many different organs. Both antigens were also found in tissue sections of various types of tumors and in the sera of the corresponding patients. Thus, organ specificity could not be demonstrated. Sensitivity of CA 19-9 was found to be high for pancreatic carcinomas, i.e., 88% of the tumors expressed the antigen shown by IH and 85% of the sera revealed concentrations above the cut-off value (greater than 37 units/ml). Evidence for CA 125 was high in ovarian carcinomas with a tissue positivity in 83% and elevated (greater than 35 units/ml) serum levels in 70% of patients. Comparing IH and RIA case by case a discrepancy was found in 14% of cases with positive IH and low serum values a vice versa. Reasons for this finding are small tumor mass not producing elevated serum levels, retention of the antigen inside the tumor cells because of defective release mechanisms demonstrable only by IH, or heterogeneity of tumors with only focal antigen expression not present in the tissue sections investigated and thus disclosable only by RIA. The relevance of immunohistochemical detection of the antigens for therapeutic planning is discussed.
In two experiments with fully-grown albino rats (Wistar strain) the energetic utilization of glucose, sunflower oil and casein in the maintenance metabolism was determined under thermoneutral conditions of keeping the animals. The relative requirement of metabolizable energy for maintenance was, with either glucose, sunflower oil or casein being the sole energy source of the feed, in experiment 1 100:105:133 and in experiment 2 100:102:135. The absolute values of the maintenance requirement of metabolizable energy were in experiment 1 347 +/- 26, 364 +/- 61 and 460 +/- 33 resp., and in experiment 2 330 +/- 11, 337 +/- 21 and 446 +/- 27 kJ/kg LW 0.75 resp. The results are discussed in connection with the efficiency of ATP synthesis (metabolizable energy/mol ATP gain) in the oxidative decomposition of nutrients.
The influence of protein in exchange for carbohydrates on the energy maintenance requirement was studied with nearly fully-grown rats at ambient temperatures between 33 and 21 degrees C. The levels of the crude protein content were 10, 25, 40 and 70%. At an ambient temperature of 33 and 30 degrees C energy maintenance requirement increased with the growing protein content in the feed. At a temperature of 30 degrees C the following values of energy maintenance requirement were measured in the sequence of the protein levels mentioned: 330 +/- 11, 347 +/- 18, 360 +/- 15 and 399 +/- 15 kJ metabolizable energy/kg live weight 0.75 X d. The occurring changes largely coincide with the expected values calculated from the efficiency of the ATP synthesis in the oxidative catabolization of protein and carbohydrates. At ambient temperatures of less than 30 degrees C, thermogenous effects after the exchange of protein versus carbohydrates could only be observed partly or not. 30 degrees C in feeding on the maintenance level and 33 degrees C in the state of hunger are estimated as the lower critical temperatures. Below the critical temperatures down to 24 degrees C heat production increased less per 1 degree C temperature decrease both in hungry and fed rats than in the temperature range between 24 and 21 degrees C. By the decrease of the ambient temperature from 24 to 21 degrees C the heat production of the hungry or fed rats increased by 39 or 33 kJ/degrees C X kg live weight 0.75 X d.
In addition to earlier experiments with growing rats on the protein levels 10, 25 and 40% crude protein in the dry matter of the feed (Hoffmann et al., 1982 a), two groups of nine male Wistar rats each received feed mixtures with 6 or 25% crude protein resp. and energy metabolism on the energy maintenance level in an N equilibrium or with a positive N balance resp. were measured on 6 levels of live weight between 65 and 250 g and additionally also at subsequent fasting day. Energy maintenance requirement on average of the 6 periods amounted to 381 and 377 kJ metabolizable energy/kg W 0.75 X d on a low or middle protein level resp. and thus did not show changes at the decrease of N retention to values of about zero even with regard to different ATP formation capacities of the nutrients.
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17 cystine stone patients were treated with high doses of ascorbic acid (5 g p. d.). During the observation period, a total of only two natural passages of cystine stones could be observed. For five patients the therapeutic strategy was altered because the recurrence rate did not change and the cystine concentration in the urine was enhanced. One mixed calcium-oxalate/cystine stone had to be resected. In this case as well as on the occasion of further medical check-ups of other patients, an increased risk of calcium-oxalate stone formation was signalled by an enhanced oxalic-acid concentration in the 24-hour urine. Changes in blood serum and impairment in hepatic and renal functions were not observed. With three patients, the therapy had to be interrupted because of gastritis symptoms. The use of high-dose ascorbic acid therapy is recommended and is continued. In special cases, an additive of low do ses of alpha-mercaptopropionyl-glycine is recommended.
The carcinogenic effects of cadmium were tested in an animal experiment to check the results of epidemiological studies showing that the incidence of prostatic carcinoma is above average in workers industrially exposed to high cadmium levels. For this purpose 1.9 mg CdCl2 (1.2 mg Cd/kg body weight) was injected into the right ventral prostatic lobe of 12-month-old male inbred rats of the Okamoto-toki strain. Simple hyperplasia was found in 38, atypical hyperplasia in 29, atypical hyperplasia with severe dysplasia in 11 and invasive prostatic carcinoma in 5 of 100 animals 270 days after the injection. Various mechanisms are discussed in connection with the carcinogenic action of cadmium.
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