Biomedical subjects
Publications and source records attributed to K D Hofmann.
In 80 pregnant women with pre-eclampsia and in 38 healthy pregnant women malondialdehyde production by blood platelets, platelet survival and several haemostatic variables were determined. It was demonstrated that due to the enhanced platelet turnover pre-eclampsia was invariably accompanied by a thrombophilic state which in severe cases developed into chronic consumption coagulopathy.
In the tissue of 54 ovarian carcinomas and 38 normal human ovaries the activity of cathepsin D was determined by means of the Anson-method. In ovarian carcinomas the mean activity of cathepsin D was 4515 pmol T/s/g tissue, in normal ovarian tissue only 2119 pmol T/s/g. The difference is significant (p less than 0,001). The dependency on age of the activity of cathepsin D suitable for normal ovary, got lost in cancer tissue. There is no relationship between the amount of activity of cathepsin D and the stage of the tumour. Extreme high activities of cathepsin D were found in metastatic ovarian carcinomas. The activity of cathepsin D is higher in endometrioid and papillary than in mucigenous and hypernephroid ovarian carcinomas. The different activities of cathepsin D were discussed with regard to the invasive growth of cancer and to deranged protein metabolism.
Lactate-dehydrogenase activities were measured from tissue homogenates of 34 human ovaries and ovarian carcinomas. Mean activities were 265.2 nmol/s/g tissue in normal ovaries and 695.1 nmol/s/g in ovarian carcinoma tissue. One and the same ratio was obtained from two comparative group of one and the same age. The above difference was significant. No relationship was found to exist between LDH activity in tumour tissue and stage of the disease.
With the aid of an asphyxia model in rabbit fetuses the possibility of diaplacental influence on the hypoxic effects of the fetal organism has been investigated. The trial to change the vasotonia during the asphyctic shock by sympathicomimetic or -lytic drugs (Dilatol, Obsidan, Ergocomb, Regitin) remained to be without any effect on the DIC in the fetal organism. Trying to seal the vascular wall by the high-molecular-weight basic polypeptide Aprotinin there seemed rather to be an increase of the intravascular fibrin sedimentation.
There is reported on the possibilities of diaplacental influencing on the DIC arising from the hypoxia we provoked with the help of an asphyxia model in rabbit fetuses. We could demonstrate the impossibility of influencing on the fetal vasal content by means of low molecular dextran, heparin or streptokinase. On the contrary, the possibility exists to influence on the fetal hemostasis by low molecular synthetic substances. The antifibrinolytic drug PAMBA causes in case of advanced acidosis diaplacental a definite growth of the intravascular coagulation, as well. But an inhibition of the fibrin sedimentation in the terminal vessels at the asphyctic shock can be achieved by applying the ethyl ester of the 4-amidinophenylpyruvic acid (APPA).
In a total of 41 rabbit fetus it could be demonstrated in an asphyxia model to what extent disseminated intravascular coagulation may be influenced by directly applying drugs in the foetal circulation. Administration of heparin or streptokinase in the umbilical vessels led to a decrease of fibrin sediments in the areas of terminal coagulation, whereas an increase was caused by injecting noradrenalin or PAMBA.
The number, proliferation, and aggregation of thrombocytes, platelet adhesiveness, and thromboblastographic values were investigated in the context of 52 women, who were on a compound hormonal contraceptive with threefold-differentiated gestagen, and of ten women with a compound hormonal contraceptive of two-fold gestagen differentiation. Tests were conducted over six months. Significant deviations from normal values were recordable. No definite conclusions, however, can be drawn from such individual observations. Disorders in thrombocyte function and change in thromboblastographic values, when considered with all their implications, are likely to suggest the presence of effects from hormonal contraceptives. Yet, both type and concentrations of oestrogens and gestagens are of minor importance to such change. Nevertheless, somewhat higher risk of thrombo-embolism should be assumed, if other conductive factors are present, at the same time.
Comparative chemical tests, under laboratory conditions, of 20 newborns with normal pH and 20 children with acidotic pH values in blood obtained from the umbilical artery have shown that in newborns medium acidosis resulted frequently is disseminated intravascular coagulation, whereas advanced acidosis led to the same situation with regularity. The thrombocytes, coagulation factors II and V, of the authors' acidotic newborns were clearly exposed to consumption. Thrombin time, partial thromboplastin time, and reptilase coagulation time were prolonged with significance. All coagulation parameters were found to correlate linearly with the postnatal pH values. Systematic efforts to detect disseminated intravascular coagulation should be made in all cases in which the postnatal umbilical artery pH of newborns in 7.09 and below. Determination of haematocrit, thrombocyte count, and fibrinogen degradation products may be sufficient as an immediate-action minimum programme in such cases.
In artificially hypoxic rabbit foetuses, rising hydrogen ion concentration with excessive precipitation of fibrin in the microcirculation, with pH values between 7.0 and 6.9, was followed by discontinuation of DIC on account of predominant regular occurrence of secondary fibrinolysis. Such processes of secondary fibrinolysis, which could be inhibited by para-amino methylbenzoic acid (PAMBA), were found to be capable of re-opening completely the circulatory tracks in surviving foetuses. In other cases, they might persist beyond death and cover up pathologico-anatomic findings, if neglected.
Application of uninvolved propanidid-infusion anaesthesia to a rabbit in advanced pregnancy is reported in this paper. Uteroplacental circulation was found to be but slightly affected. The condition of the foetuses, consequently, may be considered sufficiently safe for intra-uterine experiments.
The levels of ascorbic acid were measured in the tissue of 53 ovarian carcinomas and compared to concentrations in normal human ovarian tissue. The mean ascorbic acid concentrations per gram of tissue was 218 microgram in carcinoma tissue and 382 microgram in intact ovarian tissue. The difference was significant, with p less than 0.001. A relationship was found to exist between ascorbic acid concentrations in tumor tissue, on the one hand, stages of the disease, on the other. The importance of ascorbic acid to tumour growth is discussed.
The effects of subacute intra-uterine hypoxia on the haemostatic system of 205 foetuses from 49 pregnant rabbits were studied by a standardised experimental arrangement, with particular reference being made to intravascular precipitation of fibrin. The asphyxial shock thus induced was accompanied by almost all the rabbit foetuses by disseminated intravascular coagulation by which the central organs were more strongly affected, as compared to peripheral organs also restricted by the shock. The pathophysiological processes which were found to take place in the lungs and placentas of the experimental animals proved different from those in man, which was attributable to species-related differences.
First intravascular coagula were detected as early as in the pre-acidotic phase of artificially hypoxic rabbit foetuses used by the authors in experimental studies. Growing acidosis in circulating blood has been accompanied by excessive increase of fibrin precipitation in the terminal blood track. Further increase of intravascular coagulation was found to be discontinued by predominance of secondary fibrinolysis at blood pH around 6.9. Rising hydrogen ion concentration, as a reflection of a consumptional reaction, was found to be accompanied by decline in both the fibrinogen level and thrombocyte count in the foetal blood, fully in parallel with the above DIC.
We investigated the effect of the synthetic low-molecular thrombin inhibitor 4-amidinophenyl-pyruvic acid (APPA) on the maternal and fetal coagulation at 10 far advanced in pregnancy sheep. APPA inhibits as well the maternal as by diaplacental passage the fetal hemostasis in dependence on the dosage till the incoagulability. The effect in the fetal organism occurs after a delay of some minutes and wars of a bit earlier.
Plasma activities of the fibrin-stabilising factor (Factor XIII) were tested in 60 women who were on hormonal contraceptives, different in composition (Non Ovlon and Gravistat). The activities in either group were reduced with significance, notwithstanding steroid levels. Unambiguous interpretation of that reduction proved impossible.
Studies were conducted into 55 rabbits and their 327 foetuses to measure the two intravenously applied anaesthetics, Sombrevin and Hexobarbital, for their passage through the placenta and for the concentrations which eventually settle in various organ systems of the foetuses. Fast placental passage, but in different concentrations, was established for either anaesthetic. Sombrevin was found to reach the foetal organism only in low quantity and for short-time retention, whereas Hexobarbital passed the placental barrier in much higher concentration to stay detectably for a longer period of time in the foetal blood. While Sombrevin was not recordable from foetal organs, its intraplacental buildup reached higher concentrations. Relatively high concentrations of Hexobarbital were recordable from both the placenta and vital foetal organs. The conclusions so far derived from those animal experiments seem to suggest a superiority of Sombrevin over Hexobarbital and regard to applicability to obstetric anaesthesia.
Beta-glucuronidase activity was recorded from the tissue of 45 ovarian carcinomas and compared to the activity in normal human ovarian tissue. Mean activities were 1442 micrograms Ph./h/g tissue in ovarian carcinomas and 574 micrograms Ph./h/g in intact ovarian tissue. No relationship was found to exist between the amount of beta-glucuronidase activity and the stage of the disease.
The plasma activity of fibrinstabilizing factor (factor XIII) in 27 women treated with Non-Ovlon an anticonceptive agent, were investigated. It was found significant differences of levels plasma activity. Conclusions from isolated observations are not possible.