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R Kaaja

Publications and source records attributed to R Kaaja.

At least 37 records · Page 2Linked to original sources
PubMed1999

Evidence of a state of increased insulin resistance in preeclampsia.

Similarities in certain biochemical variables between preeclampsia and the insulin resistance syndrome imply a possible link between insulin resistance and preeclampsia. We measured insulin sensitivity by the minimal model technique between 29 and 39 weeks of gestation in 22 preeclamptic and 16 control women, whose glucose tolerance was first confirmed as normal by an oral glucose tolerance test. In addition, we measured the fasting levels of serum C-peptide, uric acid, lipids, and lipoproteins. Preeclamptic women showed a higher insulin response (P = .001) during the oral glucose tolerance test than the controls. Insulin sensitivity in preeclamptic women (1.11+/-0.15 x 10(-4) x min(-1) x microU/mL) was 37% lower (P = .009) than in control women (1.77+/-0.19 x 10(-4) x min(-1) x microU/mL). The free fatty acid (FFA) concentration in preeclamptic women (0.17+/-0.01 g/L, P = .0004) was 70% higher than in control women (0.10+/-0.01 g/L). Also, baseline serum levels of C-peptide, uric acid, and triglyceride were higher in preeclamptic women. Insulin sensitivity increased fourfold to fivefold within the first 3 postpartum months, but insulin sensitivity in preeclamptic women was still 26% lower (P = .04) than in control women. Preeclampsia is a state of increased insulin resistance, and it persists for at least 3 months after pregnancy. This may be a pathogenetic factor in preeclampsia and may contribute to the excess cardiovascular morbidity among women with prior preeclampsia.

Adult↗
PubMed1999

Plasma homocysteine levels elevated and inversely related to insulin sensitivity in preeclampsia.

OBJECTIVE: To study the plasma levels of homocysteine in preeclampsia and relate them to insulin sensitivity. METHODS: In association with a 3-hour intravenous glucose-tolerance test (glucose 0.3 g/kg at 0 and 0.03 IU insulin 20 minutes later), we measured plasma levels of homocysteine, vitamin B12, and folic acid in 22 women with preeclampsia and 16 controls between 29 and 39 weeks' gestation. In 14 women with preeclampsia and 11 controls, plasma samples also were collected 3 months after delivery. RESULTS: Levels of homocysteine in women with preeclampsia (6.7 +/- 0.4 micromol/L, mean +/- standard error) were higher (P < .001) than those in controls (3.8 +/- 0.2 micromol/L) and related significantly to the level of proteinuria (r = .49, P = .02). Vitamin B12 concentrations were lower in women with preeclampsia (166.0 +/- 10.4 compared with 212.4 +/- 16.4 pmol/L, P = .02), whereas levels of folic acid showed no difference between the groups. After delivery, levels of homocysteine increased to 9.1 +/- 0.6 and 8.2 +/- 0.6 micromol/L in women with preeclampsia and controls, vitamin B12 increased to 298.8 +/- 28.6 compared with 334.9 +/- 24.0 pmol/l, and folic acid decreased to 10.6 +/- 2.0 compared with 7.9 +/- 0.8 nmol/L, with no difference emerging between the groups. In women with preeclampsia but not in controls, plasma homocysteine was negatively related to insulin sensitivity (r = -.51, P = .02). The mean 2.9-fold increase in glucose or 52.5-fold increase in insulin during the insulin-sensitivity test failed to affect homocysteine levels. CONCLUSION: Women with preeclampsia have high plasma homocysteine levels that are inversely related to insulin sensitivity.

Adult↗
PubMed1999

Serum activin A and inhibin A elevated in pre-eclampsia: no relation to insulin sensitivity.

OBJECTIVE: To assess the possible role of serum levels of activin A, inhibin A and pro-alpha inhibin (pro-alphaC) in insulin sensitivity in pre-eclampsia. DESIGN: A prospective study. SETTING: Helsinki University Central Hospital. PARTICIPANTS: Twenty-two nulliparous women with proteinuric pre-eclampsia and 16 healthy nulliparous controls in the third trimester of pregnancy. METHODS: Serum samples were collected before and after intravenous injection of glucose (0.3 g/kg) and insulin (0.03 IU/kg) (the minimal model for testing insulin sensitivity), and were assayed for activin A, inhibin A and pro-alphaC. MAIN OUTCOME MEASURES: Comparison of the levels of activin A, inhibin A and pro-alphaC between pre-eclamptic and healthy pregnant women, and the association of these proteins with insulin sensitivity. RESULTS: In pre-eclampsia elevated levels of activin A (139%, P = 0.0001), inhibin A (39%, P = 0.003), and pro-alphaC (92%, P = 0.0008) were observed. The amount of proteinuria (0.3-10.5 g/day) correlated positively with serum concentrations of activin A (P = 0.01) and inhibin A (P = 0.02). These glycoproteins were not associated with insulin sensitivity either in women with pre-eclampsia or controls. A 2.9-fold rise in blood glucose and a 52.5-fold rise in insulin during testing using the minimal model were not accompanied by any significant changes in activin A, inhibin A, and pro-alphaC. CONCLUSION: Activin A, inhibin A, and pro-alphaC are elevated in pre-eclampsia but do not appear to relate to the insulin sensitivity in pre-eclamptic or normal pregnancies.

Activins↗
PubMed1999

Role of HLA in congenital heart block: susceptibility alleles in mothers.

In congenital heart block (CHB), abnormal maternal immunisation leads to autoantibody production against SS-A/Ro and SS-B/La antigens. These maternal antibodies are transferred across the placenta to the unborn child and are believed to transmit irreversible immunological injury in developing foetal heart tissue, thus causing 3rd-degree atrioventricular block. The mothers may suffer from systemic lupus erythematosus (SLE) or primary Sjögren's syndrome (SS), but they may be asymptomatic. Women with primary SS show a typical autoimmune HLA antigen pattern, namely higher frequency of HLA B8 and DR3 than in the normal population. The HLA pattern may affect individual ability to resist infecting bacteria and viruses and to response in various ways to autoantigens. It is probable that other factors such as genetic regulation of immune response are involved in CHB. We compared the HLA class I and class II alleles of mothers having CHB children with those of women suffering from primary SS and having healthy children, and with those of healthy Finns. Antibodies against 52-kD and 60-kD SS-A/Ro and 48-kD SS-B/La antigens were compared between the two groups of mothers. Our results show that anti-SS-A/Ro antibody-positive mothers all show a strong association with known autoimmune-predisposing HLA alleles, however, the mothers of CHB children differ in some HLA class I alleles, and especially in HLA haplotypes, from mothers of healthy children. Mothers with HLA A1, Cw7, B8 and without B15 are at particularly high-risk of having CHB children.

Alleles↗
PubMed1999

Role of HLA in congenital heart block: susceptibility alleles in children.

Congenital heart block (CHB) is a syndrome of uncertain pathogenesis leading to cardiac conduction disturbances in the foetus and newborns. It has been proposed that maternal antibodies transmit immunological injury in the developing foetal heart, thus causing irreversible damage of the atrioventricular node, leading to third-degree atrioventricular block. However, some genetic or environmental factors may also be involved. We have searched for genetic markers that play a role in immune response and that would be pathognomonic for the disease, either in mothers by regulating their immune response or in children by affecting antigen presentation and target for the maternal immune response. We have compared HLA class I and II alleles of the children with their mother and with healthy individuals and searched for HLA markers that would be emphasized in children. We have shown that particular DQ alleles in the child predispose to CHB, perhaps serving as antigen-presenting molecules on site. In addition, the HLA-Cw3 allele is involved, although its function remains to be clarified. In our results, children with CHB were often identical to their mothers in alleles of DRB, DQA and DQB loci, thus affecting foetomaternal recognition and suggesting that cell-mediated mechanisms could be involved in the pathogenesis.

Adult↗
PubMed1998

Effects of transdermal nitroglycerin on impedance to flow in the uterine, umbilical, and fetal middle cerebral arteries in pregnancies complicated by preeclampsia and intrauterine growth retardation.

OBJECTIVE: We studied whether transdermal nitroglycerin, a donor of nitric oxide, affects uterine, umbilical, and fetal cerebral blood flow in pregnancies complicated by preeclampsia and impaired uteroplacental blood flow. STUDY DESIGN: Seventeen patients with preeclampsia were treated with a nitroglycerin patch, 10 mg per 24 hours, for three consecutive days between 28 and 36 weeks' gestation. The uterine, umbilical, and fetal middle cerebral artery pulsatility index and resistance index were assessed by color Doppler ultrasonography before the start of treatment, daily during treatment, and on the first 2 days after the removal of the last patch. RESULTS: The nitroglycerin patch caused a significant fall in the mean uterine pulsatility index and resistance index that reached its maximum (18% +/- 4% and 17% +/- 3%, respectively, from baseline) on the last treatment day. After the removal of the last patch, uterine pulsatility index and resistance index rose to the pretreatment value within 12 hours. No significant changes in umbilical or middle cerebral artery pulsatility index and resistance index were observed during treatment. Maternal mean arterial pressure fell from 122 +/- 8 to 117 +/- 7 mm Hg (P = .05). CONCLUSION: Transdermal administration of nitroglycerin may offer a potential for treatment for patients with preeclampsia who have increased uteroplacental impedance.

Administration, Cutaneous↗
PubMed1998

Immune-mediated congenital heart block (CHB): identifying and counseling patients at risk for having children with CHB.

OBJECTIVE: To identify patterns of maternal antibodies associated with an increased risk of having a child with congenital heart block (CHB) and to provide a basis for counseling women with a previously affected child. METHODS: This retrospective clinical study of the obstetric histories of 46 Finnish women with a CHB child compared the strength and specificity of the immune response to SS-A/Ro and SS-B/La, as determined by immunoblot and ELISA, in 44 affected women with 85 women with systemic lupus erythematosus (SLE) and 32 women with primary Sjögren's syndrome (SS) with healthy children. RESULTS: High levels of anti-SS-A/Ro and anti-SS-B/La by practically all assays were associated with a significantly increased risk of having a CHB child. The best single test to identify high-risk mothers was anti-52 kd SS-A/Ro by immunoblot (OR 18.9), and it was the only assay to detect mothers at increased risk of CHB as compared with controls with primary SS. Low risk of CHB was indicated by undetectable or low levels of antibodies in the ELISA assays and no reactivity on immunoblot. Mothers with a previous child with CHB had a history of fetal loss (mostly spontaneous abortions) or a history of recurrent fetal losses (> or = 3) slightly more often than controls. Late-trimester obstetric complications in non-CHB pregnancies were insignificant. The relative risk for a female child compared with a male child to have CHB was 1.9 (1.2-2.9, P = .009), and the risk of the mother having another child with CHB was 12% (4 of 34). CONCLUSION: Although there is no unique antibody profile specific for CHB, mothers with a high or low risk of having a child with CHB can be identified. Female children appear to have an increased risk of CHB, but the risk of the mother having another child with CHB is low.

Abortion, Spontaneous↗
PubMed1998

Insulin resistance syndrome in preeclampsia.

Because changes in lipids, lipoprotein, and other metabolic processes, such as hyperinsulinemia and hyperuricemia, found in preeclampsia resemble the main features of the insulin resistance syndrome, it has been proposed that insulin resistance may be the common denominator for such metabolic changes. Several groups, using euglycemic-hyperinsulinemic clamping or intravenous glucose tolerance tests (Bergman's minimal model technique), have demonstrated insulin resistance during late pregnancy. Women with preeclampsia had higher fasting insulin levels, but also exaggerated hyperinsulinemia, in response to an oral glucose tolerance test, which is consistent with increased insulin resistance in preeclampsia. No direct measurement of insulin sensitivity (clamp or minimal model) has as yet been performed during preeclampsia. Increased insulin resistance can activate the sympathetic nervous system and lead to an increase in expression of receptors for endothelin, both of which events lead to increased blood pressure. Hyperinsulinemia can also induce hypertriglyceridemia, leading to endothelial dysfunction and reduction of prostacyclin production. This hyperinsulinemia can persist for as long as 17 years after preeclamptic pregnancy and may contribute to a woman's increased risk of cardiovascular disease. Insulin resistance may not be the cause of preeclampsia, but is one of the pathogenic factors, especially in genetically predisposed women.

Cardiovascular Diseases↗
PubMed1998

Evidence of high circulating testosterone in women with prior preeclampsia.

Women with prior preeclampsia are characterized by hyperinsulinemia and a 2- to 3-fold excess risk of hypertension and ischemic heart disease in later life. We therefore studied whether these women present changes in pituitary, ovarian, and endothelial factors that could also affect the risk of vascular disorders. Twenty-two women with prior preeclampsia and 22 control women matched by age and body mass index were studied an average of 17 yr after delivery. Women with prior preeclampsia had elevated serum free testosterone levels (20.6 +/- 2.2 vs. 15.0 +/- 1.3 pmol/L, mean +/- SE, P = 0.03), an elevated free androgen index (3.2 +/- 0.5 vs. 1.9 +/- 0.2, P = 0.04), and an elevated free testosterone estradiol ratio (0.089 +/- 0.017 vs. 0.046 +/- 0.006, P = 0.02). The levels of insulin-like growth factor binding protein-1 decreased as expected during a 3-h oral glucose tolerance test without differences between the groups. Levels of FSH, LH, androstenedione, dehydroepiandrosterone sulfate, and endothelin-1, as well as urinary output of prostacyclin and thromboxane A2 metabolites, showed no difference between study groups. A history of preeclampsia an average of 17 yr earlier thus appears to be associated with elevated levels of testosterone, which may contribute to the increased risk of vascular morbidity in such women.

Adult↗
PubMed1997

Contrast sensitivity in diabetic pregnancy.

PURPOSE: To evaluate the correlation between the changes in contrast sensitivity and retinopathy throughout pregnancy in diabetic women with mild background diabetic retinopathy. METHODS: Contrast sensitivity (Vistech 6500 Contrast Test System) was measured in 22 type I diabetic women with mild background retinopathy [0-16 microaneurysms (MAs)/eye and occasional small intraretinal hemorrhages] and 10 healthy pregnant women at the 12th and 32nd weeks of pregnancy and 3 months after delivery. Red-free fundus photography was also performed at all visits. RESULTS: Throughout pregnancy contrast sensitivity was lower in the diabetics than in the controls at 1.5, 3.0, and 6.0 cycles per degree (cpd). During the course of pregnancy, contrast sensitivity decreased at 1.5 and 6.0 cpd in patients with more than five new MAs compared to those with fewer than five new MAs during pregnancy. Likewise, contrast sensitivity decreased at 6 cpd in patients with an increase in MA count during pregnancy and at 6 and 12 cpd in patients with a baseline MA count of two or more MAs. CONCLUSIONS: Contrast sensitivity, especially at low to mid-range spatial frequencies, is decreased in diabetic women with mild retinopathy. Even small changes in retinopathy are reflected in a decrease in contrast sensitivity during and after pregnancy. Thus, contrast sensitivity seems to be a sensitive indicator of changes in minimal background retinopathy.

Adult↗
PubMed1997

The effect of pregnancy on mild diabetic retinopathy.

PURPOSE: To study microaneurysm (MA) formation and disappearance rates during pregnancy and postpartum in diabetic women with mild diabetic retinopathy. METHODS: Red-free photographs were taken at the 12th, 24th and 32nd-36th weeks of pregnancy and 3 and 6 months postpartum from 21 type 1 diabetics with mild diabetic retinopathy. In a subset of 13 patients follow-up was continued until 1 year after pregnancy. Fundus photographs were analysed using a computer-assisted fundus lesion localization system. RESULTS: In the whole material the total MA count was 3.1 +/- 3.6 (mean +/- SD) at the 12th week, 3.4 +/- 3.1 at the 24th week, 4.1 +/- 4.9 at the 32nd-36th week, 5.4 +/- 6.2 at 3 months postpartum and 5.2 +/- 5.8 at 6 months postpartum. We found that MA count increased during pregnancy, but it was highest 3 months postpartum. Both the rate of MA formation and the rate of MA disappearance increased during pregnancy, with the disappearance rate exceeding the formation rate 6 months postpartum. In patients having mean HbA1c levels below the median value of 6.38 mmol/l there was a flare-up of MAs during pregnancy, levelling by 3 months postpartum. Patients with a higher than the median (0.76 mmol/l) decrease in HbA1c level compared to pre-pregnancy HbA1c also developed more MAs during the course of pregnancy. CONCLUSIONS: These data suggest that there is continuous turnover of MAs during pregnancy. MA count increases during pregnancy but the MA count was highest 3 months postpartum, after which the formation rate started to decline. Temporary aggravation of mild retinopathy occurs in diabetic patients after normalization of blood glucose levels.

Adult↗
PubMed1997

Congenital heart block: HLA differences between affected children and healthy siblings in four Finnish families.

Congenital heart block without intracardiac anatomic malformations is a potentially lethal disease affecting children and newborns. The mother often has an autoimmune disorder with autoantibodies against SS-A/Ro and/or SS-B/La antigens. However, only a minority of the children of these mothers develop complete heart block. It is believed that the maternal antibodies are pathogenic, but other immunological mechanisms such as cell-mediated injury cannot be excluded. Maternal cells may recognize fetal antigens adjacent to fetal HLA, and thus some children may be more susceptible to heart block than others, depending on their HLA genetics. The purpose of this study was to evaluate whether there are HLA differences between children with heart block and their healthy siblings. Six affected children in four families and their siblings were studied. MHC class I were typed serologically and class II and some non-HLA alleles were typed by DNA techniques. DQB1*03/04 were seen more often in the affected children than in the siblings. Some other differences were also seen in the other antigens of the MHC area.

Alleles↗