Recurrent deep venous thrombosis in pregnancy.
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Biomedical subjects
Publications and source records attributed to K Klein.
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Platelet function (ADP-induced platelet aggregation) in 20 patients with juvenile-onset diabetes mellitus was not different from that of age- and sex-matched controls. Platelet sensitivity to exogenous PGI2 was not diminished in diabetic patients. No sex differences were detected. There was no correlation between concomitant blood glucose levels and platelet sensitivity to PGI2.
The increase of a serum protein in the circulation of rats following partial hepatectomy or the injection of thyroid hormone (T3) is reported. This serum protein factor is present in normal rat serum and accounts for approximately 1% of the total serum protein. The protein disappears from the serum of animals bearing Morris hepatomas 7777 or 7800. The amount of serum protein factor diminishes as the tumors increase in size. The levels of this protein in the serum fall immediately following partial hepatectomy. At 24 hours following the operation, however, the levels are increased well over those found in normal rats. Increased levels persist for 12 days following partial hepatectomy. The serum protein is also increased following injections of T3 and is decreased in thyroidectomized animals. Elevated levels of T3 are correlated with elevated levels of the serum protein and both are correlated with increased hepatic DNA synthesis. Low levels of T3 are followed by low levels of serum protein resulting in a diminished capacity for hepatic DNA synthesis. Injection of purified serum factor into normal rats results in increased [3H]thymidine incorporation in liver cells. It is suggested that the synthesis of this serum protein is stimulated by T3 and DNA synthesis is influenced by the serum protein. The serum protein might be a humoral factor influencing metabolic events in hepatocytes or hepatomas or it might be a carrier for an agent that in turn has a direct effect on these tissues.
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Based on 2450 hemodynamic-vascular examinations by means of atraumatic techniques (particularly ultrasound vascular echography, Doppler-flowmetry, dynamographical circulation analysis, impedance cardiography) on 1242 stationary and ambulatory patients the capacity of a riskless angiological program aiming at practice and therapy is resumed. Due to their high validity and accuracy the methods proved to be not only screening and selection base for the use of special invasive measurements, but also self-supporting requirement for the respectively adequate rehabilitative management and therapeutic consequences in circulation and cardiovascular diseases. The registrated findings, especially in stenosis of the carotid and vertebral arteries, cerebral arteriosclerotic processes, hypertensive and hypotonic syndromes, orthostatic, vegetative and stress-induced dysregulations, differential diagnosis of cephalic troubles (e.g. headache, dizziness and so on), in peripheral arterial and venous disorders as well as in cardiocerebral problems, were evaluated effectively and integrated into the clinic and basic research.
The activation of platelets due to foreign surface interaction is a well known fact. Earlier, we found an increase of circulating platelet microaggregates (method of Wu and Hoak) during hemodialysis. Since this phenomenon might cause a PGI2-release by lung and/or vascular tissue, we studied the plasma 6-oxo-PGF 1 alpha-levels in 6 patients during hemodialysis. We found an initial increase of plasma 6-oxo-PGF 1 alpha. Coincidently, hypoxemia, fall in platelet and lekocyte count and a decrease in platelet count ratio were observed. An effect of heparin was excluded in a control group. The findings support the hypothesis that PGI2 acts as a defense mechanism against platelet deposition on vascular wall by a temporary increased synthesis which could be monitored by a temporarily enhanced plasma 6-oxo-PGF 1 alpha-level during the initial phase of hemodialysis.
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The synthesis of prostacyclin (PGI2), the most potent known inhibitor of platelet aggregation, varies with age. After 30 years the production decreases, but increases again in the 6th and 7th decade. Contrary to these physiological variations patients suffering from juvenile onset diabetes or peripheral angiopathy show a markedly decreased prostacyclin synthesis. Since the prostacyclin system in thought to be an important blood vessel protector, the pathological low level of PGI2-synthesis could be a key position in development or progression of vascular complications.
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PGs and GAGs have been isolated from fresh bovine aortas according to the method of Hascall and chemically characterized. These PGs and GAGs had only little effects on ADP- and collagen-induced platelet aggregation, but had very potent inhibitory action on thrombin-induced platelet aggregation and prolonged thrombin-clotting-time. Of the standard GAGs investigated hyaluronic acid, chondroitin-4-sulfate and chondroitin-6-sulfate had only little inhibitory action on thrombin-induced platelet aggregation, whereas heparin was very potent in this respect. The unsaturated disaccharides originating after degradation of GAGs with chondroitinases had no effect on platelet aggregation. No differences between PGs and GAGs in inhibiting thrombin-induced platelet aggregation could be detected.
Heparin had no effect on PGI2-activity if heparin and PGI2 have been incubated-together in an ice bath for 3 minutes. But heparin was able - unlike the other Pg or GAG - to abolish PGI2-activity if it had been incubated with PGI2 in an ice bath for 15 minutes. Pg and GAG, which had been isolated from bovine aortas according to the method of Hascall, and commerically available GAG (hyaluronic acid, chondroitin-40-sulfate, chondroitin-6-sulfate and heparin) had no effect on PGI2-formation of rat aortas in short time incubation (3 min). After long time incubation (15 min) or rat aortas in heparin less PGI2 was detectable compared to a buffer incubation. These data suggest that Pg and GAG do not influence PGI2-formation of arteries. The diminished PGI2-activity after long time incubation should be due to the PGI2-degrading effect of heparin.
An artificial vessel replacement, which is athrombogenic and impermeable for a migration from the adjacent tissue, was implanted end to end into the thoracic aorta of 10 sheep. The center of this tube has a Dacron surface, which is known to trap blood elements. We examined the tissue samples built up by blood derived cells between 2 and 84 days morphologically by means of light microscopy as well as by SEM and TEM. We checked the thrombus fragments of 7 cases for their PGI2-generation using MONCADA's bioassay. In our specimens we found an average activity of 4, 7 pg PGI2 mg/min. The morphological examination revealed different stages of thrombosis and organization consisting of a large number of cells. Macrophages, fibroblast like cells, myofibroblasts as well as endothelial cells and foreign body giant cells around the Dacron fibers could be found. Our experimental design excludes the ingrowth of mesenchymal elements, which suggests that blood derived cells are able to produce PGI2.
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3,3',5-Triiodo-L-thyronine (200 microgram/100 g) is shown to be a potent liver parenchymal cell mitogen in the rat, and thyroidectomy is seen to severely inhibit hepatocyte proliferation in regenerating rat liver. Taken together, these observations point to a crucial role for the iodothyronine in liver cell hyperplasia. The growth rates of the transplantable Morris hepatomas 7777 and 5123tc are shown to be retarded in the surgically thyroidectomized-parathyroidectomized rat. This inhibition of tumor growth can be reversed by thyroid hormone administration. It has earlier been observed that the hypothyroid state induced in the rat by administration of propylthiouracil or radioactive iodine retarded the growth of the transplanted Morris hepatomas 7800 and 44, suggesting that these tumors were also thyroid dependent. Our results suggest that the thyroid hormones may play a similar role in the growth of liver cell-derived cancers as they do in normal hepatocyte proliferation.
In haemodialysis an interaction between platelets and the dialysator membrane occurs, which is not prevented by heparin. This can be demonstrated by parietal depositions of platelets in the capillaries of the artificial kidney by scanning electron microscopy, as well as in a marked increase of reversible platelet microaggregates during the first phase of dialysis. Some patients are prone to develop thrombosis of the capillary kidneys in spite of a high-dose heparinization. In these cases the use of diclofenac, a cyclooxygenase inhibitor, prevents these adverse platelet reactions.
In rehabilitation, patients suffering from stenosing processes of cerebral vessels represent a particular target group with particularly difficult diagnostic and therapeutic problems. On the basis of own experiences it was possible to test on 25 persons (age: 37 to 83 years) suffering from carotid and vertebral stenosis the capability of the cerebral vessels echography--alone and in combination with the DOPPLER flowmetry--:. This highly valuable cerrebrovascular screening method coupled with clinical findings makes it possible to give a more definite indication for angiography, and represents under certain circumstances (inoperability or undue strain in the presence of a reduced general and vascular status) a safe alternative to invasive methods. The modern programs involving in-patient rehabilitation and, in particular, vasoactive, blood pressure stabilising and cardiac protection accentuating long-term treatment were all successful--notwithstanding the sometimes very severe and prognostically unfavorable neurological involvement, the frequent associated internistic diseases, the risk factors and the intercurrent complications: All rehabilitants (age: 37 to 73 years) were discharged partly or fully mobile (6 in each case) following on average a 55-day stay in this ward. In each case it was possible to achieve a distinct improvement in the cerebral functional disorders, the subjective state and general condition, as well as a high degree of social reintegration.
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