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Biomedical subjects

K Bremme

Publications and source records attributed to K Bremme.

At least 55 records · Page 3Linked to original sources

The long-term outcome of proximal vein thrombosis during pregnancy is not improved by the addition of surgical thrombectomy to anticoagulant treatment.

OBJECTIVES: To compare the long-term outcome for pregnant/puerperal women with iliofemoral venous thrombosis treated either with thrombectomy and additional anticoagulants or with anticoagulants alone. DESIGN: Retrospective study of two treatment methods. MATERIALS: Thirty women with iliofemoral venous thrombosis during pregnancy or puerperium were treated with thrombectomy and additional anticoagulants. Twenty-five women, with the same condition, treated with anticoagulants only were obtained from a registry. The mean follow-up time for both groups was 9 years. The patients of the two groups were well matched, had the same risk factor score and were comparable except for duration of symptoms before treatment. METHODS: The follow-up comprised history and clinical examination, colour Duplex ultrasound and venous strain-gauge plethysmography. RESULTS: Patency of iliac veins, symptoms of chronic venous disease, venous emptying and venous reflux did not differ between the groups. A significant reduction of outflow was found in 20% of the surgically treated patients and 16% of the controls. Impaired muscle pump function was seen in less than half of the patients in both groups. CONCLUSIONS: Surgical thrombectomy does not offer any advantage over anticoagulation treatment alone in the long-term outcome for patients with iliofemoral venous thrombosis during pregnancy or puerperium.

Adolescent↗

Arg506-Gln mutation in factor V and risk of thrombosis during pregnancy.

Seventy women with thrombosis in pregnancy were investigated for the presence of APC resistance and the associated Arg506-Gln mutation in coagulation factor V. The mutation was found in 46% of the investigated women. Carriers of the mutation were more prone to develop thrombosis in the first pregnancy (OR (odds ratio) = 3.41; P < 0.05) and had a higher probability of recurrence (OR = 3.86; P < 0.05) compared to non-carriers. The incidence of miscarriage was not related to the mutation but its probability increased in women with thrombosis in a second or subsequent pregnancy (P < 0.025). Negative dynamics of APC response during pregnancy was observed in 20/22 women; eight of them developed APC resistance de novo. The suppression of APC response was independent of the mutation.

Adolescent↗

Flow cytometric quantitation of serum anti-D in pregnancy.

BACKGROUND: The major cause of fetal hemolytic disease is maternal immunization to D in D-incompatible pregnancies. To prevent complications, D-incompatible pregnancies are monitored for the level of maternal anti-D. At present, the monitoring of anti-D levels is performed by the indirect antiglobulin test complemented by quantitation by the technique used in an automated antibody detection and quantitation instrument. STUDY DESIGN AND METHODS: Flow cytometry was used to quantitatively determine the level of anti-D in serum and to analyze the IgG subclass distribution and the presence of IgM anti-D in these samples. The results were compared to the indirect antiglobulin test titer and to the results obtained by the technique used in an automated antibody detection and quantitation instrument. RESULTS: Flow cytometry allowed sensitive and accurate determinations of anti-D levels with low interassay and intra-assay variability, both for serum samples and standard curves. CONCLUSION: Flow cytometry is a simple, rapid, and reliable method for determining the serum levels of D antibodies and their Ig subclass distribution. It is therefore well suited for the monitoring of women during D-incompatible pregnancies.

Female↗

Hemostatic abnormalities may predict chronic hypertension after preeclampsia.

OBJECTIVES: Preeclampsia is a pregnancy-induced hypertensive disease. About 25-30% of women suffering from this disease will later, while still fertile, develop essential hypertension. STUDY DESIGN: Various hemostatic variables known to increase the risk of cardiovascular complications were investigated in 28 women with severe preeclampsia and 14 with mild preeclampsia 6-15 months after delivery. RESULTS: High levels of the coagulation inhibitors protein C and total protein S were found in the women with severe preeclampsia (p < 0.001). The levels of prothrombin complex, fibrinogen, plasminogen activator inhibitor-1 were increased in women who had previously had severe preeclampsia as compared to those who had had mild preeclampsia (p < 0.01). The levels of the four markers for thrombin activity (thrombin-antithrombin complex, prothrombin fragments 1 + 2, fibrin D-dimers and soluble fibrin) were higher in the severe preeclampsia group. In 12 women in this group (43%), the levels of three to four variables were higher than the reference ranges (mean +/- 2 SD). In patients with earlier severe or mild preeclampsia, factor VII antigen was also found to be increased as compared to normal fertile women (p < 0.02). CONCLUSIONS: Women with earlier severe preeclampsia displayed increased levels of coagulation factors and the main fibrinolytic inhibitor, high levels of which are known to predict cardiovascular events. This was also reflected by increased levels of thrombin markers.

Adult↗

Studies on phospholipid antibodies, APC-resistance and associated mutation in the coagulation factor V gene.

The influence of antibodies against phospholipids (PLa) on APC response was investigated in 155 women with a history of thromboembolism and/or repeated foetal losses. PLa were determined as antibodies against cardiolipin (CLa) and phosphatidyl serine (PSa) and as lupus anticoagulant (LA) tested by dilute Russell's Viper Venom time and by the Textarin/Ecarin ratio. APC-response was studied by a clotting (aPTT-based) and by an amidolytic (factor IXa-X-based) assay. A reduced response to APC (APC-resistance) was found in 49% of 65 PLa-positive and in 13% of 90 PLa-negative samples (chi 2 = 23.9; p < 0.5 x 10(-4)). It was more common in the samples with LA, as compared to CLa+PSa positive (58% vs. 30%, not significant). The presence of the mutation causing Arg506-Gln substitution in coagulation factor V was investigated in 84 samples. The occurrence of the mutation in APC-resistant patients with CLa+PSa or with LA in one of the two assays was similar to those without PLa (84% and 100%, respectively). In the absence of APC resistance, the occurrence of the mutation was similar in the samples with and without PLa (14% vs. 11%). Samples with LA, determined by both tests used, comprised a special group where the frequency of the mutation in the APC resistant samples was significantly reduced (p < 0.01). In the latter samples, the pathogenic mechanism of APC resistance may be connected with the influence on phospholipid membranes.

Abortion, Habitual↗

Phospholipid antibodies and resistance to activated protein C in women with thrombophilia.

Seventy-eight women with a history of thromboembolism were studied for cardiolipin antibodies (CLa), lupus anticoagulant activity (LA) and resistance to activated protein C (APC-resistance). Elevated CLa were found in 15 (19%) and LA in 15 women (19%), respectively. Twenty-six patients (33%) were APC-resistant, 17 of them had LA and/or CLa. No correlation was observed between the LA coefficient, CLa level and the extent of APC-resistance. The study shows the difference in the nature of phospholipid antibodies (PLa) and APC-resistance: cause-dependent for APC-resistance and time-dependent for the LA activity. APC-resistance was commoner in thrombosis triggered by endogenous (pregnancy, delivery) than by exogenous (oral contraceptives, surgery) factors (P < 0.05). The incidence of PLa was not connected to the cause of thrombosis. Time-dependent changes in the PLa spectrum manifested by a reduction of isolated LA frequency five years after thrombosis (P < 0.05). The response of APC seemed to show no variation with time passed after thrombosis. The co-existence of PLa and APC-resistance in 22% of thrombophilic women may stress the role of phospholipids in the blood coagulation process.

Adult↗

Increased blood flow resistance in placental circulation and levels of plasminogen activator inhibitors types 1 and 2 in severe preeclampsia.

To study whether increased resistance in the placental circulation changes the plasma levels of plasminogen activators types 1 and 2 (PAI-1 and PAI-2) in severe preeclampsia, the levels of PAI-1 activity and PAI-2 antigen were determined in 33 severely preeclamptic and 22 normal pregnant women during gestational weeks 24-35. In the preeclampsia group, the Pulsatility Index (PI) of the umbilical artery was investigated with Doppler ultrasound. The levels of PAI-1 activity were higher (P < 0.01) whereas those of PAI-2 antigen were lower (P < 0.01) in the preeclampsia group than in the normal pregnancy group. The patients with abnormally high PI (high PI group) had increased PAI-1 levels (P < 0.05) and unchanged PAI-2 levels (P > 0.05), compared with those with normal PI (normal PI group). The levels of PAI-1 were positively correlated to the PI values during pregnancy weeks 34-35 only in the high PI group (r = 0.88, P < 0.05). In conclusion, high resistance in the placental circulation elevates plasma PAI-1 activity levels but does not influence PAI-2 antigen levels.

Female↗

Increased concentrations of lactate dehydrogenase in pregnancy with preeclampsia: a predictor for the birth of small-for-gestational-age infants.

Lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations and platelet counts were measured in 26 normal pregnant women and 51 preeclamptic women. In the normal-pregnancy group, no significant changes were found in the results of these tests. In the preeclampsia group, ALT and AST concentrations were not significantly higher than those in normal pregnancy, but the LDH concentrations increased and the platelet counts decreased significantly through the pregnancy. The increases in LDH did not correlate with changes in ALT or AST. Preeclamptic women with small-for-gestational-age (SGA) infants had significantly higher LDH concentrations than those in the appropriate-for-gestational-age (AGA) group, but ALT and AST concentrations did not increase significantly. As reasons for the LDH increase in our subjects, liver damage was excluded and more active glycolysis in addition to severe cell damage due to chronic anoxemia were inferred. It is suggested that an increase in LDH is predictive of SGA infants in preeclamptic pregnancy, especially in those with normal liver function.

Alanine Transaminase↗

Midmolecular parathyroid hormone-related peptide in serum during pregnancy, lactation and in umbilical cord blood.

Indications of an important physiological role of parathyroid hormone-related peptide (PTHrP) for fetal calcium homeostasis, maternal-fetal calcium transport and reproduction have accumulated over recent years. The PTHrP concentrations were measured by an earlier developed midregion radio-immunoassay in serum from lactating healthy females and umbilical cord blood and compared with levels in age-matched non-pregnant or lactating females. The PTHrP concentrations could be measured in all samples after silica cartridge C18 extraction of 10-12 ml of serum. The concentrations were significantly higher during lactation (mean +/- SD: 0.72 +/- 0.14 pmol/l, N = 22) and in umbilical cord blood (0.85 +/- 0.18 pmol/l, N = 12) compared with healthy age-matched women (0.48 +/- 0.09 pmol/l, N = 10, p < 0.001). The molecular forms of PTHrP were also studied in an age-matched control group, in pregnant women and in umbilical cord blood by gel chromatography in a fast protein liquid chromatography system of Sep-Pak-extracted pooled serum. In all three groups we found heterogeneity of the molecular forms with two predominant peaks. The smallest fragment had a molecular weight of 4-6 kD while the largest form appeared as a high-molecular-weight molecule. In conclusion, the concentrations of midmolecule PTHrP fragments in serum are elevated during lactation and in umbilical cord blood. Because the midregion of PTHrP has unique actions, our results indicate that PTHrP may play an important physiological role for the mother and for the maternal-fetal calcium transport.

Chromatography, Liquid↗

Thrombotic risk factors and oral contraception.

Eighty-one women with a history of thrombosis were classified into three groups: group I (n = 29), women in whom thrombosis developed during oral contraception; group II (n = 33), those who used oral contraceptives (OC) without complications but experienced vascular occlusion in other risk situations; group III (n = 19), women who never used OC. The level of antibodies to anionic phospholipids (PLa), a response to activated protein C (APC), and the presence for the mutation in the coagulation factor V gene causing APC resistance were studied. In the studied groups, APC resistance was present in 14% to 42% of patients. PLa were elevated in about half of APC-resistant patients. The incidence of APC resistance correlated with the recurrency of the thrombotic events within the groups. In most cases it was tightly connected to the mutation in the factor V gene. Women in whom thrombosis developed while they were taking OC (group I) differed from the others, having a remarkable disagreement between the lowest incidence of APC resistance and a relatively increased number of the mutation (14% vs 38%, p < 0.025). This finding suggested that the APC response is flexible. An influence of OC that predisposes a reduction in APC response is discussed.

Adolescent↗

Long-term development for girls and boys at age 16-18 as related to birth weight and gestational age.

The present study was based on data from a longitudinal research program which consisted of 12,032 children, born in the Stockholm area in 1953 of which there were 494 children born with low birth weight (LBW, 2500 g or less). For all children at age 16 it was apparent that adjustment and psychiatric disturbances as well as juvenile delinquency were not related to birth weight and gestational age. LBW girls born at term, had significantly lower school grades, at age 16, than NBW (normal birth weight) girls. NBW boys born pre-term had lower school grades than NBW boys born at term. It is suggested that childhood development is gender related; in girls the birth weight--and in boys the length of the pregnancy was related to school marks at age 16. For boys at 18 years of age at the military draft, it was shown that LBW boys had smaller body size and lower IQ-test scores as compared to NBW boys. Additionally the length of the pregnancy was related to some measures of body size but not to IQ-test scores.

Adolescent↗

Do lowered factor VII levels at extremely high endogenous oestradiol levels protect against thrombin formation?

The purpose of the study was to find a model to study the effect of endogenous oestradiol on haemostasis. Hormones and haemostatic variables were therefore measured before and after in vitro fertilization and egg replacement therapy in 14 women with tubal infertility. The differences between the levels of the haemostatic variables at minimum and maximum levels of oestradiol and progesterone were evaluated. A significant increase in the plasma levels of coagulation factor VIII, von Willebrand factor and fibrinogen was found between samples drawn before stimulation and at the highest oestradiol levels (P < 0.002, P < 0.002 and P < 0.015, respectively). However, coagulation factor VII activity and antigen decreased significantly (P < 0.001 and P = 0.009, respectively). The levels of the coagulation inhibitors protein C and antithrombin decreased (P < 0.003 and P = 0.008, respectively), while that of free protein S increased (P = 0.039). No significant changes were observed in the fibrinolytic variables or in those reflecting thrombin activity (prothrombin fragment 1 + 2, thrombin-antithrombin complexes, soluble fibrin and D-dimers). In conclusion, the increase in the levels of factor VIII, von Willebrand factor, fibrinogen and the decrease in the levels of antithrombin and protein C may, if coagulation is triggered, contribute to a hypercoagulable state. The depressed factor VII levels and the tendency to elevated free protein S levels may constitute a protective mechanism that modulates the coagulation system when levels of oestradiol become extremely high.

Blood Coagulation Disorders↗

Growth hormone-binding protein in plasma is inversely correlated to placental lactogen and augmented with increasing body mass index in healthy pregnant women and women with gestational diabetes mellitus.

Pituitary growth hormone (GH), prolactin (PRL), placental lactogen (PL), insulin-like growth factor 1 (IGF-1) and GH-binding protein (GHBP) in plasma were determined in 12 women with gestational diabetes mellitus (GDM) and in 12 healthy pregnant women during a breakfast meal tolerance test. The women with GDM showed higher prepregnancy weight, body mass index (BMI), basal levels of glucose, insulin, and C peptide compared to the pregnant controls. No difference was found between the two groups in pituitary GH, PRL, PL and IGF-1 levels. Plasma levels of GHBP were higher in the women with GDM compared to pregnant controls. In all women there was an inverse correlation between PL and pituitary GH as well as between PL and GHBP, suggesting that PL inhibits pituitary GH secretion. A positive correlation between GHBP and BMI was found in all women, and the higher BMI in the GDM women seemed to be the cause of the higher GHBP levels in this group. In all women IGF-1, an indicator of the secretory activity of lactogenic hormones as well as of nutritional state, showed a positive correlation with the birth weights of the infants and was equally indicative in both groups.

Adult↗

Plasma levels of von Willebrand factor and fibronectin as markers of persisting endothelial damage in preeclampsia.

OBJECTIVE: To evaluate the levels of von Willebrand factor and fibronectin as markers for the severity of endothelial cell injury in preeclampsia. METHODS: In 63 pregnant women with preeclampsia, the plasma levels of von Willebrand factor and fibronectin were measured as soon as symptoms were detected, at 5 weeks postpartum, and after lactation. They were also compared with levels in 29 normotensive pregnant women. The von Willebrand factor was measured by enzyme-linked immunoassay and fibronectin was measured using an automated immunonephelometric method. RESULTS: In preeclampsia, the levels of von Willebrand factor and fibronectin were higher than in normal pregnancy samples drawn in the second and third trimesters. The levels of fibronectin were still elevated at 5 weeks postpartum in women with severe preeclampsia. Four patients with severe preeclampsia who were studied frequently had high levels of von Willebrand factor 5 weeks postpartum. CONCLUSIONS: The increased maternal plasma levels of von Willebrand factor and fibronectin indicate that endothelial stimulation is present during preeclampsia. The high fibronectin values found even 5 weeks after delivery, at least in patients with severe preeclampsia, may indicate an ongoing vascular disease with increased risk for preeclampsia in subsequent pregnancies.

Adult↗

Is oxytocin involved in the deterioration of glucose tolerance in gestational diabetes?

The present study assessed the possible role of oxytocin in the deterioration of glucose tolerance in gestational diabetes. Plasma levels of oxytocin, insulin, glucagon and glucose were measured at the time of a 400-kcal breakfast meal tolerance test in 12 women with gestational diabetes and 12 normal pregnant women in the third trimester. The gestational diabetic women had higher basal levels of insulin and an enhanced, delayed and prolonged insulin response to the breakfast. The same differences occurred in the glucose levels. There was no significant difference in the glucagon levels between the two groups. In the normal pregnant women, a significant (p < 0.05) though small rise in glucagon levels occurred 30 min after the ingestion of the breakfast. Oxytocin levels were not affected by the breakfast, and there was no clear difference between the two groups. The metabolic differences between the normal pregnant and gestational diabetic women were not related to any differences in oxytocin levels. In conclusion, we found no evidence of a role of oxytocin in the alteration of glucose metabolism in women with gestational diabetes. However, since alterations in oxytocin levels of possible significance for an impaired glucose tolerance are found in type 1 diabetic and extremely obese patients, further studies are needed in women with gestational or manifest diabetes.

Adult↗

Women with prolactin-producing pituitary adenoma show decreased serum placental lactogen during pregnancy.

Prolactin (PRL), growth hormone (GH), placental lactogen (PL), chorionic gonadotropin (CG), estradiol (OE), progesterone (P4) and sex hormone-binding globulin (SHBG) were measured in serum throughout gestation in 9 women with PRL-producing pituitary adenomas. They had been treated at least 1 year with the dopamine agonist bromocriptine before pregnancy occurred. All women bore healthy babies of normal birthweight. Their PRL levels did not show the successive increase seen in normal pregnancies; serum PRL was unphysiologically increased in all patients up to the 20th week of gestation, whereafter PRL levelled off and fell within the normal range. Serum PL levels were lower in the women with prolactinoma compared to healthy pregnant women, despite normal placental weight. The serum GH levels in the patients determined with an immunoassay based on a monoclonal antibody, were low or nondetectable, similar to healthy pregnant controls. In contrast, high molecular weight GH in serum as determined with a monoclonal antibody which also recognizes PL appeared to be increased in comparison with healthy pregnant women. The serum levels of CG, OE, P4 and SHBG were all within the normal range. These results show that the unphysiological secretion of PRL in pregnant women with PRL-producing pituitary adenomas is associated with decreased serum levels of PL.

Adult↗

The effect of prophylactic heparin treatment on enhanced thrombin generation in pregnancy.

OBJECTIVE: To assess the activation status of blood coagulation in thrombosis-prone pregnant women receiving a reduced dosage of heparin. METHODS: Forty-three women were given subcutaneous heparin treatment during pregnancy; the dosage was monitored so that the heparin (anti-Xa) level was within the stipulated range of 0.08-0.15 anti-Xa units 3 hours after injection. Several coagulation variables were investigated and some routine analyses were performed. The results were compared with those of a control group of 26 healthy pregnant women. RESULTS: Compared with the control values, hemoglobin (P < .01), fibrinogen (P < .05), and total protein S (P < .01) were increased already before heparin treatment was started and continued to be increased significantly throughout pregnancy. During heparin treatment, protein C levels (P < .01) and the factors measured by prothrombin time (P < .001) were increased compared with the controls. Antithrombin decreased, though not as much as when patients are given therapeutic dosages. The fibrinolytic inhibitors behaved as in normal pregnancy. Three variables measuring thrombin formation or coagulation activation (ie, thrombin-antithrombin complexes, D-dimers, and soluble fibrin) were increased in a high proportion before heparin treatment was started; they normalized somewhat during treatment. CONCLUSIONS: In early pregnancy, women with previous thrombotic episodes have high plasma levels of coagulation variables and of markers of coagulation activation compared with controls. Such changes may be used to predict the need for treatment and, in the future, to control treatment.

Adult↗