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[Alpha 1 fetoprotein in pre-eclamptic toxemia (author's transl)].

From 1973 to 1975, 287 serum levels of alpha 1 fetoprotein in women with pre-eclamptic toxemia were determined. Pre-eclamptic toxemia was classified according to modified scheme of Goecke and Rippmann. 161 patients had mild pre-eclamptic toxemia (index 1-3), 72 patients had moderate pre-eclamptic toxemia (index 4-6), 54 patients had severe pre-eclamptic toxemia (index 7). In all types of severity of pre-eclamptic toxemia more levels of alpha fetoprotein were lower or higher than the normal levels including the standard deviations. The number of abnormal values rose with an increasing toxemia index. There was no statistically significant difference between too high values and too low values. Significantly more values were above and also below the normal values. Our investigations appear to indicate that the determination of the alpha fetoprotein is not only valuable as screening method for neural tube defects but also of value in the diagnosis and management of pre-eclamptic toxemia. Too high and too low values should not be differentiated but values both above and below the normal levels should be considered.

Adolescent

Diet-related toxemia in pregnancy. I. Fat, fatty acids, and cholesterol.

Toxemia in pregnancy (preeclampsia)is characteristerized by a combination of at least two of the following clinical symptoms: hypertension, edema, and proteinuria. In three successive trials over three consecutive years, the dietary intake of a selected number of young pregnant women attending a Maternal and Infant Care Program at Tuskegee Institute were evaluated for total lipids, individual fatty acids, and cholesterol. Women with toxemia or with any of the individual symptoms were identified and women without toxemia or these symptoms served as controls. Results were variable from repetition to repetition in all but the toxemia group and the edema group. The consumption of total lipids and cholesterol was significantly greater in all three trials by both the toxemia and edema groups. Also, total saturated, monounsaturated, and polyunsaturated fatty acids were eaten in greater amounts. The greatest differences were in palmitic acid, stearic acid, oleic acid, and linoleic acid. The proportion of unsaturated fatty acids consumed in all groups was very low. All differences could be attributed primarily to breakfast and dinner meals and were found in the milk, meat, and egg food groups. Although satistical correlations were found between lipid intake and toxemia of pregnancy any specific relationship between the two is still unclear.

Adolescent

An experimental study on "replantation toxemia". The effect of hypothermia on an amputated limb.

Hind legs of dogs were amputated at the middle of the thigh and preserved in three different conditions: in ice water, in a refrigerator, and at room temperature. After 6 or 12 hours of ischemia, recirculation was established. The survival rate of the animals was observed and measurement of limb edema, potassium, pH, and lactate in the blood was performed to study the effects of hypothermia on prevention of "replantation toxemia." Cooling of the amputated limb was effective for prevention of toxemia, and the cooling effect was greater in ice water than in a refrigerator. However, when cooled in ice water, some animals died due to toxemia when the time of ischemia was prolonged to 12 hours. In the dead animals, a close relationship was observed between the developement of toxemia and metabolic acidosis due to the increase in lactate.

Amputation, Surgical

Placental lesions in experimental toxemia in the rabbit.

Unlike the normal human placenta, the normal rabbit placenta, near term, is essentially free of such stigmas of aging as infarcts and syncytial knots. When experimental toxemia is produced in the pregnant rabbit by ligating the terminal aorta to a specific degree of stricture, placental lesions resembling those found in human toxemia are observed; namely, diffuse congestion, old and recent infarcts, and syncytial knots. All the treated animals who exhibited anatomical and clinical signs of toxemia presented, in association, obvious placental lesions; there were, however, some animals which showed infarct but no other signs of toxemia.

Animals

Experimental toxemia in the pregnant primate.

In order to develop a model for the study of eclamptogenic toxemia, a series of experiments were carried out on 31 female baboons. In Group 1, consisting of 10 animals, metal clips were placed around the uterine arteries in order to partially occlude them, and the ovarian vessels were transected. The animals were subsequently mated. Nine developed hypertension and proteinuria, and one aborted. The renal lesions in these animals were indistinguishable from those described in human toxemia. Group 2 consisted of three of the 10 baboons from Group 1, which became pregnant a second time. They again developed hypertension and proteinuria. In Group 3, three baboons at 100 days of gestation were treated as in Group 1 with similar results. Groups 4 and 5 served as pregnant (3) and nonpregnant (15) controls. It is concluded that a toxemia model has been developed in a subhuman primate. This model will prove useful in the further study of eclamptogenic toxemia.

Animals

Studies on lipoperoxide of normal pregnant women and of patients with toxemia of pregnancy.

1. Serum lipoperoxide was determined by the method of Yagi et al. (Yagi, K., Nishigaki, I. and Ohama, H. (1968) Jap. J. Vitamin 37, 105) for 22 cases of non-pregnant women, 24 cases of 1st trimester of pregnancy (1-12 weeks), 39 cases of 2nd trimester of pregnancy (13-26 weeks), 58 cases of 3rd trimester of pregnancy (27-40 weeks), and 30 cases of toxemia of pregnancy (27-40 weeks). Remarkable increases of lipoperoxide were observed at 2nd and 3rd trimester of pregnancy compared with non-pregnant women, and the increase in toxemia of pregnancy was more remarkable than that at 3rd trimester of pregnancy. In umbilical cord blood a higher level of lipoperoxide was observed in patients with toxemia of pregnancy than in normal pregnant women. 2. The total TBA value determined by extracting the serum-lipids with chloroform and methanol solution showed a similar tendency to the above. 3. Those showing TBA-reaction by the analysis of lipids with thin-layer chromatography were the fractions of cholesterol ester, triglyceride and phospholipid. While triglyceride fraction showed a marked increase of TBA value during pregnancy and in toxemia of pregnancy.

Female

The differential diagnosis between preeclamptic toxemia and glomerulonephritis in patients with proteinuria during pregnancy.

The renal biopsies from 123 patients who presented with proteinuria during pregnancy have been reviewed. Forty-seven showed glomerulonephritis that could be diagnosed on morphological grounds or on a clear-cut history of urine abnormalities before pregnancy. Fifty of the remaining 76 had been followed after pregnancy. In these 50 patients, a retrospective diagnosis of glomerulonephritis or preeclamptic toxemia was based on the persistence or disappearance of proteinuria and/or hematuria three or more months after pregnancy. Among 22 in whom a biopsy diagnosis of "pure" preeclamptic toxemia had been made, 19 showed disappearance of urine abnormalities after pregnancy, thus confirming the biopsy diagnosis. A retrospective analysis showed focal and segmental glomeris group but none in the preeclamptic toxemia group. Other differences could not be defined without quantitative evaluation; however, the glomeruli appeared to be more cellular in the glomerulonephritis group. The presence of IgA, IgG, IgM, Complement, and fibrin was not of value in distinguishing glomerulonephritis from preeclamptic toxemia.

Arteries

[Present day status in therapy of toxemia of pregnancy (author's transl)].

Since the causes of toxemia of pregnancy are unknown, therapy is still symptomatic and is now determined by the most recent knowledge of the pathophysiology of the disease. Rest, a balanced, predominantly protein-rich diet and avoidance of stress are recommended as prophylactic treatment of toxemia of pregnancy in patients with a predisposition of the condition. Early recognition of the symptoms of toxemia of pregnancy is of great importance. Treatment of mild cases consists of bed rest, possibly supplemented by sedatives and a preponderantly proteinrich diet. Administration of diuretics is obsolete and sodium restriction is no longer recommended. Antihypertensives are seldom indicated. Overweight women are no longer maintained on specially low calorie diets. Severe cases of toxemia of pregnancy must be trated as inpatients under intensive care. Principles of treatment are: 1. Prevention of seizures (by sedation). 2. Improvement of the general condition of the women (especially circulation and renal function). 3. Delivery at an opportune time for mother and child. Treatment of eclampsia follows largely the same principles. In these cases, immediate delivery is required regardless of the condition of the fetus.

Anticonvulsants

[Cytophotometric determination of DNA concentration in the nuclei of the human placental trophoblast in late toxemias of pregnancy].

The distribution of trophoblast nuclei of the human placenta by their ploidy was studied in normal pregnancy and in late pregnancy toxemias by the monowave emthod of cytophotometry in visible light. In the plasmodiotrophoblast a pronounced increase in the amount of nuclei in the S-phase (up to 40%) was noted in late toxemias which suggests a considerable activation of the DNA synthesis. The placenta cytotrophoblast in late toxemias is substantially different from that in normality. The Langhans cells disappear almost completely while in normality they are present in young terminal villi till the very end of pregnancy. The amount of the island cytotrophoblasts is much greater, the distribution of nuclei according t the DNA content being of absolutely different character than in normality. A great amount of hypodiploid nuclei (up to 36%) was observed which are absent in normal conditions as well as much greater fluctuations in the amount of diploid nuclei (from 4% to 37%) as compared with the normal amount (25.9%). These data show a high amitotic activity in the island cytotrophoblast in late toxemias. The above changes in the plasmodiotrophoblast and cytotrophoblast might be considered as a compensatory reaction of the placenta to a considerably increased vacuolization and deep atrophic processes in degenerating villi.

DNA

[Effect of a polyvalent proteinase inhibitor from the lungs of a bull on the state of the kinin system in burn shock and acute burn toxemia].

Effect of a polyvalent inhibitor of proteinases from bovine lungs (industrial preparation -- ingitrile, commercial grade -- conntrical) on the state of kinin system was studied in blood serum of patients with extensive burns at shock periods and in acute burn toxemia. Decrease in content of kallikreinogene, which is typical for shock and acute, toxemia and which reflects the activation of kallikrein-kinin system, was less distinct in patients, treated with the inhibitor, than in patients, which were not treated with ingitrile. The early and rapid restoration in kininogene content and distinct inhibition of the total arginine-esterase activity were observed in blood serum after treatment with the inhibitor. The inhibitor did not affect the phase alterations in the carboxypeptidase N activity within the first 3 days after the burns; the distinct decrease in the enzymatic activity was confirmed within the first period of the burn shock. Within 24-48 hrs after the burns content of alpha1-antitrypsin was distinctly increased in patients treated with ingitrile as compared with the untreated group. The data obtained suggest that the polyvalent proteinase inhibitor causes a decrease in activity of the kallikreinkinin system in blood plasma and affects the enzymes participating indirectly in formation of kinins in burned patients. The data obtained are in agreement with the distinct clinical effect of the inhibitor. The doses of the inhibitor used in these studies did not cause normalizing effect on the activity of the kinin system components and on the clinical state of patients only in extremely severe cases of burn shock and in acute burn toxemia with letal outcome within the few days after the injury.

Acute Disease

Plasma renin and aldosterone in an abdominal pregnancy with toxemia.

The first reported measurement of plasma renin and aldosterone in toxemia with an abdominal pregnancy is presented. In contrast to toxemia where plasma renin and aldosterone are either normal or low, extraordinarily high levels of both were found in this patient which returned to normal after delivery. The role of extrarenal renin in the hypertension of toxemia is discussed and the possibility raised that the elevated renin in this case was of placental origin.

Adult

Immunologic aspects of term pregnancy toxemia. A study of immunoglobins and complement.

IgA, IgG, and IgM were measured by the single radial immunodiffusion method in umbilical cord and maternal sera in toxemia patients and in normal term pregnant cases. Complement (C' 3) levels were determined only in maternal sera. Quantitation of IgA, IgG, and IgM was performed in concentrated serial urine samples from three eclamptic and three normal control patients. Results show that there are lower IgG and IgM levels in the sera of mothers with toxemia of pregnancy; however, paradoxically higher IgM levels were detected in cord sera from their newborn infants without evidence of placental leakage or increased neonatal infection. The finding of the low IgG and IgM levels appears to be due in part to immunoglobin loss into the urine. The unchanged complement levels in toxemia, in this study, are not suggestive of an active immunologic process, but the high IgM in the newborn infants of toxemic mothers is unexplained and may represent active immunologic disease. Clearly, investigations of tissue binding and the formation of immunoglobin complexes should be carried out to better explain these abnormal findings.

Blood Protein Electrophoresis

Production of experimental toxemia in the pregnant rabbit.

Experimental toxemia of pregnancy was induced in 51 of 122 rabbits by constriction of the aorta below the renal arteries. The approach was extraperitoneal and dependent on the accuracy in calibrating this stricture between 0.6 and 1.0 mm. Experimental toxemia in the rabbit was characterized by hypertension, proteinuria, weight gain, and reduced weight of the fetus. Blood pressure and blood flow studies distal to the aortic constriction demonstrated a marked diminution of blood supply below the constriction. The light microscopic changes in the kidneys and in the liver were similar to those of human toxemia. The electron microscopic changes consisted of endothelial swelling and subendothelial deposits. In a separate experiment, 22 pregnant rabbits near term had an aortic constriction varying between 0.6 and 1.0 mm. This constriction lasted 4 to 12 days. Glomerular deposits of fibrinogen were demonstrated by immunofluorescence in 20 of 22 animals. The intensity of the immunofluorescence was related to the severity and duration of the aortic stricture.

Animals

Renal prostaglandins for induction of labour-a dual clinical advantage in toxemia of pregnancy.

Prostaglandin A is known to be an antihypertensive vasodepressor agent produced by the kidney and has the basic potentialities of a hormone. No information is available at present concerning its effect on the human pregnant uterus and whether it can be used as an oxytocic compound to induce labour. The uterine stimulating and labour inducing ability of PGA1 was evaluated in 10 cases; seven patients were suffering from pregnancy toxemia while three were normal pregnancies near full term. Cardiotocographic tracings showed that uterine activity was markedly stimulated to a degree sufficient to induce labour. Continuous i.v. infusions at a rate of 0.25-1.0 mug/Kgm/min given over a fixed period of only 6 hours resulted in delivery in all cases except one following the discontinuation of administration. Beneficial effects on blood pressure were observed in toxemic subjects. Potentially serious FHR patterns and occasional hypertonus during therapy were seen and stress the need for more information to evaluate the safety, optimum dosage and duration of infusion as well as the place of this approach in clinical practice for the management of pregnancy toxemia. The absence of antidiuretic effect, the hypotensive response and uterine stimulating property of PGA1 indicate a possible advantage in toxemia of pregnancy as compared to oxytocin infusions.

Blood Pressure

Effect of prostaglandin A1 on renal hemodynamics in pregnancy toxemia.

PGA1 was infused at a constant rate for 2 hours in 35 pregnant women in the third trimester. Twenty-five patients had clinical manifestations of pregnancy toxemia and 10 served as control subjects. Two dose levels (0.5 to 1.0 mug/kg/min) were investigated and obstetric aspects as well as renal hemodynamics were evaluated. At the high-dose level, the drug induced labor in half the subjects (toxemia patients and control subjects) and elicited a hypotensive response only in hypertensive cases. A marked increase in GFR and RPF was achieved at both dose levels in all cases. Plasma electrolytes, osmolality, and urea levels were unaltered. Also, the infusions did not induce any appreciable diuresis or natriuresis. Tph mechanisms of the induced changes and possible etiologic involvement of PGA1 in toxemia are discussed.

Blood Pressure