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[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 Administration of diuretics is obsolete and sodium restriction is no longer recommended.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 Overweight women are no longer maintained on specially low calorie diets.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↗

[Serum unconjugated 2-hydroxyestrone and erythrocyte catechol-O-methyltransferase activity in pregnancy toxemia].

To clarify the significance of catecholestrogens in toxemia of pregnancy, plasma unconjugated 2-hydroxyestrone (2-OHE1) was measured by a specific radioimmunoassay. In addition, catechol-O-methyltransferase (COMT) activity in erythrocytes was compared between normal and toxemic pregnancies. The following results were obtained. There was no significant difference in the plasma 2-OHE1 level between normal and toxemic pregnancies in the 3rd trimester, these being 220 +/- 53(SD,n = 7), 162 +/- 138(n = 9) pg/ml, respectively. However, the plasma 2-OHE1, level was quite low in all three subjects in toxemic pregnancy with placental dysfunctions. Liver dysfunction was found in only one case of toxemic pregnancy, whose plasma 2-OHE1 was within the normal range. In two cases of mild toxemia and one case of severe toxemia with placental dysfunctions there was no significant difference in COMT activity as compared with normal pregnancy. The COMT activity of a diabetic woman with pregnancy toxemia without placental dysfunctions was slightly higher than that of a normal pregnant woman. From these results it is suggested that the lower plasma 2-OHE1 level in toxemic pregnancy may be caused by placental dysfunctions.

Catechol O-Methyltransferase↗

[Acute central neurologic complications and the pregnancy-puerperal status. 105 cases in an intensive care unit. Contribution to the study of the relation between pregnancy toxemia and cerebral vascular accidents].

Central neurological pathology in the course of puerperium was studied in 105 observations. One could distinguish: --meeting pathology (tumoral, metabolic, infectious processes) 12 cases, --cerebral vascular accidents (arterial, venous...) 30 cases, These two groups corresponded to a pathology without any obvious connection with gravidic toxemia. --eclamptic or not eclamptic toxemia with encephalopathy: 21 cases, --finally, toxemia associated to or complicated with focused neurological syndromes: 42 cases. Concerning cerebral vascular accidents, one could verify the importance of hemorrhagical accidents (13 cases: 3 subdurhematoma, 4 sub-arachnoid hemorrhages, 6 intra-cerebral hematoma (2 of them corresponded to previous affections revealed by the hemorrhage) (angioma, chorioepithelioma, metastases) and thrombo-embolic accidents (16 cases) corresponding especially to arterial thromboses, the frequency of which seems more important than the frequency of venous thromboses. Any generalized or focused central neurological accident sets the problem of toxemia but is not obligatory toxemic. An associated disorder of hemostasis (hypercoagulability, consumption coagulopathy) has to be searched for.

Acute Disease↗

Coagulation, fibrinolysis, platelet and kinin-forming systems during toxemia of pregnancy.

The coagulation, fibrinolysis, and platelet and kinin-forming systems were studied during toxemia of pregnancy by multifactorial examinations. In severe toxemia of pregnancy, decreases in extrinsic coagulation factors, platelet, antithrombin III, plasminogen, alpha 2-plasmin inhibitor, and increases in soluble fibrin-monomer complex, fibrin degradation products, beta-thromboglobulin were observed. This suggests that intravascular coagulation, induced probably through the extrinsic pathway and secondary fibrinolysis, is associated with toxemia of pregnancy. Prekallikrein increased during pregnancy but decreased rapidly with onset of labor. The same changes were observed in high molecular weight kininogen, indicating that kinin may be generated, which would contribute to the uterine contraction during labor. The prekallikrein level was significantly low during severe toxemia.

Blood Coagulation↗

Severe energy restriction in treatment of toxemia of pregnancy.

A total of 78 patients with toxemia pregnancy were treated for over a week before delivery. The treatment was characterized by (1) mental and physical rest, (2) disuse of hypotonic, diuretic, and antispasmodic agents, and (3) a diet with reduced salt and energy (200-1200 Cal/day). Except for one fetal death, which occurred during delivery, all mothers and their babies left the hospital in good condition. No fetal or neonatal deaths that were related to the maternal condition or severity of toxemia were encountered. The long-lasting complications of toxemia were lower than those reported by others. No critical accident was noted. Our treatment proved to be efficient in the treatment of toxemia.

Adult↗

[A study for predicting toxemia of pregnancy by the diastolic notch in pulsed Doppler flow velocity waveforms of the uterine arteries--quantitative analysis of the diastolic notch as uterine arterial index (UTAI)].

To investigate the ability of measurement of the diastolic notch in Doppler flow velocimetry to predict development of toxemia of pregnancy, analysis of uteroplacental and fetal blood flow waveforms was performed. The waveforms were analyzed by calculating the resistance index (RI) and the pulsatility index (PI) and were investigated whether diastolic notches existed or not. In the prospective study, the uterine arterial index (UTAI; an index introduced to evaluate the degree of diastolic notch quantitatively) was also calculated. RETROSPECTIVE STUDY: The waveforms in the uterine arteries, the umbilical artery and the fetal vessel (inferior vena cava, descending aorta and middle cerebral artery) were measured in 153 pregnant women. PROSPECTIVE STUDY: Uterine artery velocimetry was performed at 16-23 weeks' gestation in 387 pregnant women. RESULT 1: Subjects with a diastolic notch had significantly higher rates of development of toxemia of pregnancy. Indexes of the fetal blood flow waveforms had no significant correlations with the development of toxemia of pregnancy. RESULT 2: UTAI showed an equivalently high negative predictive value (98.1%) and higher positive predictive value (17.6%) than RI (98.2%, 10.2% respectively) and PI (98.7%, 12.7% respectively). CONCLUSION: UTAI measurement was more useful for predicting toxemia of pregnancy than RI or PI.

Arteries↗

[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↗

A fluorescence method for estimation of toxemia: binding capacity of lipoproteins and albumin in plasma.

The hazard of toxemia, a condition resulting from the spread of toxins by the bloodstream, is regulated by plasma proteins capable of binding with free toxins. As toxin binding results in a reduction of available binding sites, measuring the proteins' binding capacity can be used to estimate toxemia severity. Suggested by this approach, a novel fluorescence method was developed to determine lipoprotein and albumin binding capacities in whole plasma. The method entails two steps: specific binding of N(n-carboxy)phenylimide-4-dimethyl-aminonaphthalic acid with albumin followed by addition of 12-(9-anthroyloxy)stearic acid which, under these conditions, binds mostly with lipoprotein. Reduced fluorescence intensity of the probes in plasma of patients compared to that of healthy donors reflected saturation of binding sites by toxins, thereby estimating toxemia severity. Poor correlation was found between the lipoprotein and albumin binding abilities, suggesting their independent diagnostic values. The simplicity and rapidity of this method are advantageous for its clinical application.

Adult↗

[Staphylococcal and streptococcal pediatric toxic syndrome from 1998 to 2000. Data from the National Center for Staphylococcal Toxemia].

The clinical and microbial settings of staphylococcal and streptococcal toxemia in pediatric patients were investigated by the French National Reference Center for Staphylococcal Toxemia. From 1998 to 2000, the number of cases was low in regard to the usual putative incidence of these toxemia; this low incidence was probably linked to the passive collection of cases. The most significant finding was the evidence of skin infections as the source of the majorities of staphylococcal toxic shock syndrome and staphylococcal scarlet fever as described for streptococcal toxic shock syndrome or nosocomial suppurative infections. Moreover, most of scalded skin syndrome were from pediatric patients and were exceptional in adults. For other syndromes, no significant original findings were observed.

Adolescent↗

THE PATHOGENIC ROLE OF FIBRIN DEPOSITION IN THE GLOMERULAR LESIONS OF TOXEMIA OF PREGNANCY.

An immunofluorescent study of renal biopsies from patients with toxemia of pregnancy has been performed. It was found that the glomeruli consistently showed bright staining for fibrin within endothelial cells, as well as occasional deposits along the basement membrane. Gamma globulin was only occasionally demonstrable, generally in the form of irregular deposits along the basement membrane. beta(1C) was absent and albumin was not seen in glomeruli, except sometimes in the form of droplets within epithelial cells. In biopsies from pregnant patients without toxemia only equivocal staining for fibrin was seen. On the basis of these observations and other evidence discussed, it is proposed that the accumulation of fibrin in glomeruli reflects a prolonged state of intravascular clotting in toxemia and that the arrest in glomeruli of some form of circulating fibrin constitutes the basic pathogenic mechanism of the glomerular damage in this disease.

Basement Membrane↗

[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↗

The amylase/creatinine clearance ratio in normal pregnancy and pregnancies complicated by pancreatitis, hyperemesis gravidarum, and toxemia.

The Cam/Ccr% has been suggested to be of value in the diagnosis of pancreatitis. The Cam/Ccr% was determined throughout gestation in normal pregnant and nonpregnant patients. The Cam/Ccr% was lower (p less than 0.05) throughout pregnancy and was a function of increased creatinine clearance. The Cam/Ccr% was increased in pregnant patients with pancreatitis. Two of four patients with the clinical diagnosis of hyperemesis gravidarum demonstrated elevations of the Cam/Ccr%. Toxemia with epigastric pain was noted to be associated with an elevated CamCcr% in all patients, whereas toxemia without epigastric pain was not routinely noted to be associated with an elevated ratio. The normal Cam/Ccr% in pregnancy is lower than the nonpregnant value, and this should be taken into consideration when evaluating a patient with suspected pancreatitis who is pregnant. Patients with the clinical diagnosis of hyperemesis gravidarum and toxemia should be screened with serial Cam/Ccr% for possible evolving pancreatitis.

Adult↗

Experimental induction of a toxemia-like syndrome in the pregnant beagle.

A toxemia-like syndrome was induced in pregnant beagles by intraperitoneal inoculation of concentrates prepared from placentas of patients with preeclampsia-eclampsia and hydatidiform mole, which contained an agent, Hydatoxi lualba, that stained in a unique fashion with toluidine blue-O-. The pregnant dogs inoculated with either of these concentrates progressively developed hypertension, eyeground changes consistent with hypertensive retinopathy, proteinuria, disseminated intravascular coagulation, and hepatic dysfunction in addition to intrauterine growth retardation and intrauterine fetal death. Hepatic periportal hemorrhage and glomeruloendotheliosis, lesions usually seen in preeclampsia-eclampsia, were also noted to occur in pregnant beagles inoculated with these concentrates. A significant increased sensitivity to angiotensin II infusion was also noted. The toxemia-like syndrome did not develop in pregnant beagles when inoculated in a similar fashion with concentrates prepared from placentas from normal term pregnancies which were free of Hydatoxi lualba or in nonpregnant beagles inoculated with concentrates containing Hydatoxi lualba. Although the agent was not injected in pure form, the inoculation of concentrates containing Hydatoxi lualba appears to be required for the manifestation of the toxemia-like syndrome.

Angiotensin II↗

Clinical applications of the altered iron kinetics of toxemia of pregnancy.

The previously reported elevation of serum iron in association with toxemia of pregnancy was evaluated to determine if this chemical test could be clinically useful. When patients with toxemia and pregnant women with chronic hypertension were compared, a serum iron value greater than 100 micrograms/dl or an increase greater than 70% above baseline was a sensitive and specific indicator of toxemia. The predictive value is high and exceeds that of other commonly available tests. The clinical value of this model is discussed.

Female↗

Amniotic fluid human chorionic gonadotropin in late pregnancy: elevated levels in toxemia with intrauterine growth retardation.

Amniotic fluid human chorionic gonadotropin (hCG) was studied by radioimmunoassay in 88 normal pregnancies and in 48 pregnancies with toxemia either with or without intrauterine growth retardation, between 34 and 41 weeks. In normal pregnancy, no significant change in the hCG level was observed from 34 to 41 weeks, with the logarithmic mean value being 522 mU/ml. The hCG levels in amniotic fluid were markedly elevated in toxemia (logarithmic mean 1,079 mU/ml), especially when associated with intrauterine growth retardation (logarithmic mean 2,056 mU/ml). Since in intrauterine growth retardation without maternal disease the hCG levels were normal (logarithmic mean 657 mU/ml), toxemia itself may be the factor that causes elevated levels of hCG in amniotic fluid.

Amniotic Fluid↗