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Biomedical subjects

Risto Kaaja

Publications and source records attributed to Risto Kaaja.

14 recordsLinked to original sources
PubMed2003

Major malformations in offspring of women with epilepsy.

BACKGROUND: The offspring of women with epilepsy are at an increased risk of major congenital malformations, but the impact of the various contributing factors remains unresolved. METHOD: In 1980 through 1998, the authors prospectively followed up 970 pregnancies in women with epilepsy at a single maternity clinic. Of their 979 offspring, 740 were exposed to maternal antiepileptic drugs (AED) during the first trimester of pregnancy and 239 were not exposed. Maternal AED levels and serum folate concentrations were measured at the end of the first trimester. Logistic regression analysis was applied to identify factors associated with the occurrence of major malformations in the fetuses and newborns. RESULTS: Major malformations were detected in 28 fetuses (3.8%) exposed to maternal AED and in 2 (0.8%) not exposed (p = 0.02). After logistic regression analysis, the occurrence of major malformations was independently associated with use of carbamazepine (adjusted OR 2.5; 95% CI 1.0 to 6.0), use of valproate (4.1; 1.6 to 11), use of oxcarbazepine (10.8; 1.1 to 106), low serum folate concentration (5.8; 1.3 to 27), and low maternal level of education (3.0; 1.3 to 6.8). Major malformations were not associated with seizures during the first trimester (0.6; 0.1 to 2.9). CONCLUSIONS: Major malformations in the offspring of mothers with epilepsy are associated with use of AED during early pregnancy, and also with low serum folate concentrations and a low level of education.

Abnormalities, Drug-Induced↗
PubMed2003

Expression of bradykinin receptors in the left ventricles of rats with pressure overload hypertrophy and heart failure.

OBJECTIVES: Bradykinin exerts cardioprotective effects through bradykinin type-2 receptors (BK-2Rs). After acute myocardial infarction in rat, the heart adapts by increasing its number of BK-2Rs. However, in human chronic end-stage heart failure, the number of BK-2Rs is significantly decreased. Thus, the presence of a cardioprotective BK-2R signaling system may be critical in the prevention of pressure overload-induced heart failure. DESIGN: To explain differences in myocardial BK-2R expression during cardiac overload, we studied: (1). spontaneously hypertensive rats (SHRs) of different ages, and (2). normotensive Sprague-Dawley rats subjected to aortic banding or angiotensin II infusion. METHODS AND RESULTS: The mRNA levels of BK-2Rs were found to be significantly (P < 0.05) increased in the aging (12 and 20-month-old) SHRs (2.9- and 3-fold, respectively). Similarly, in the Sprague-Dawley rats, the expression of BK-2Rs was increased at 12 h (1.8-fold, P < 0.05) and at 3 days (3.1-fold, P < 0.05) after aortic banding, and at 2 weeks (2.2-fold) after angiotensin II infusion. In the 12-month-old SHRs, with compensated left ventricular hypertrophy (no fibrosis or left ventricular dysfunction), the amount of BK-2Rs was also significantly increased (1.8-fold, P < 0.05). However, in the 20-month-old SHRs, with a dramatic increase in fibrosis and development of diastolic dysfunction and heart failure, the amount of BK-2Rs were significantly decreased (63%, P < 0.05) specifically in the cardiac endothelial cells. CONCLUSIONS: The present results show that, during pressure overload and compensated left ventricular hypertrophy, the expression of BK-2Rs is increased. However, ongoing pressure overload leads to a loss of BK-2Rs with a dramatic increase in left ventricular fibrosis followed by diastolic dysfunction and heart failure.

Angiotensin II↗
PubMed2003

Retinal capillary blood flow in diabetic and nondiabetic women during pregnancy and postpartum period.

PURPOSE: To evaluate the response of retinal capillary circulation to pregnancy in women with diabetes and to correlate microcirculatory changes with progression of retinopathy during pregnancy. METHODS: A prospective follow-up study of 32 pregnant women with insulin-dependent diabetes and 11 nondiabetic pregnant women. Perimacular capillary blood flow measured noninvasively by retinal flowmetry in the inferior perimacular retina. Eleven nonpregnant diabetic women served as diabetic control subjects. RESULTS: In diabetic women, blood flows, measured by small-box analysis, were 233 +/- 69 (mean +/- SD) arbitrary units (AU) during the first trimester, 248 +/- 55 AU during the third trimester, and 238 +/- 46 AU 3 months postpartum, compared with 204 +/- 32, 195 +/- 22, and 196 +/- 34 AU in nondiabetic pregnant women (P = 0.007 between groups). A difference of the same magnitude was evident between the two groups when the mean of the 50th (P = 0.032), 75th (P = 0.004), and 90th (P = 0.007) percentiles of the individual pixel flow values were used in point-wise analysis. In nonpregnant diabetic women, the small-box mean value was 201 +/- 36, and the mean of the 75th percentile value in point-wise analysis was 316 +/- 49. Blood flow was lower in nonpregnant than in pregnant diabetic women during the third trimester (P = 0.023 and P = 0.012, respectively). CONCLUSIONS: Compared with nondiabetic pregnant women, retinal capillary blood flow was higher in diabetic women during pregnancy and after delivery. Together with the hormonal and metabolic changes occurring during pregnancy, hyperdynamic retinal capillary circulation may contribute to the progression of retinopathy in pregnant diabetic women.

Adult↗
PubMed2003

Progression of retinopathy during pregnancy in type 1 diabetic women treated with insulin lispro.

OBJECTIVE: To evaluate the progression of retinopathy during pregnancy and postpartum in (insulin-dependent) women with type 1 diabetes treated with insulin lispro or with regular human insulin. RESEARCH DESIGN AND METHODS: A prospective open study of 69 pregnant women with diabetes was performed. A total of 36 of the women were treated with insulin lispro (lispro group) and 33 were treated with conventional short-acting human insulin (regular insulin group). The retinopathy level was estimated by color fundus photography every trimester and postpartum. Glycemic control during pregnancy, hypoglycemia (blood glucose level <3 mmol/l) in 24-h glucose profile, blood pressure, and proteinuria were registered. RESULTS: HbA(1c) values were similar at baseline in the first trimester but thereafter were lower in the lispro group than in the regular insulin group throughout pregnancy (P = 0.022, repeated-measures ANOVA). The number of hypoglycemic episodes did not differ between the treatment groups. In multivariable logistic regression analysis with retinopathy severity (Diabetes Control and Complications Trial level) in the third trimester as the dependent variable, only nulliparity qualified as a predictor in the model [Exp(B) = 4.0, 95% CI 1.1-13.7, P = 0.030]. Factors such as duration of diabetes, type of insulin used, mean HbA(1c) level throughout pregnancy, blood pressure (systolic or diastolic), preeclampsia in the current pregnancy, smoking, or prepregnancy planning did not explain the retinopathy progression. CONCLUSIONS: Insulin lispro improves glycemic control during diabetic pregnancy compared with regular insulin with no adverse impact on progression of diabetic retinopathy.

Adult↗
PubMed2002

Susceptibility loci for preeclampsia on chromosomes 2p25 and 9p13 in Finnish families.

Preeclampsia is a common, pregnancy-specific disorder characterized by reduced placental perfusion, endothelial dysfunction, elevated blood pressure, and proteinuria. The pathogenesis of this heterogeneous disorder is incompletely understood, but it has a familial component, which suggests that one or more common alleles may act as susceptibility genes. We hypothesized that, in a founder population, the genetic background of preeclampsia might also show reduced heterogeneity, and we have performed a genomewide scan in 15 multiplex families recruited predominantly in the Kainuu province in central eastern Finland. We found two loci that exceeded the threshold for significant linkage: chromosome 2p25, near marker D2S168 (nonparametric linkage [NPL] score 3.77; P=.000761) at 21.70 cM, and 9p13, near marker D9S169 (NPL score 3.74; P=.000821) at 38.90 cM. In addition, there was a locus showing suggestive linkage at chromosome 4q32 between D4S413 and D4S3046 (NPL score 3.13; P=.003238) at 163.00 cM. In the present study the susceptibility locus on chromosome 2p25 is clearly different (21.70 cM) from the locus at 2p12 found in an Icelandic study (94.05 cM) and the locus at 2q23 (144.7 cM) found in an Australian/New Zealand study. The locus at 9p13 has been shown to be a candidate region for type 2 diabetes in two recently published genomewide scans from Finland and China. The regions on chromosomes 2p25 and 9p13 may harbor susceptibility genes for preeclampsia.

Chromosome Mapping↗
PubMed2002

Macular capillary blood flow velocity by blue-field entoptoscopy in diabetic and healthy women during pregnancy and the postpartum period.

PURPOSE: To study macular capillary blood flow velocity in diabetic and healthy women during pregnancy and the postpartum period. METHODS: A prospective study of 46 pregnant women with insulin-dependent diabetes and 11 healthy pregnant women was performed. Macular capillary blood flow velocity was measured by blue-field entoptic simulation. Diabetic retinopathy was graded from colour fundus photographs. RESULTS: In diabetic women, the macular capillary blood flow velocity was 0.94+/-0.27 mm/s (mean +/- SD) during the first trimester, 1.00+/-0.28 mm/s during the third trimester and 1.03+/-0.24 mm/s 3 months postpartum, compared with values of 0.71+/-0.20, 0.77+/-+/-0.20 and 0.82+/-0.19 mm/s, respectively, in healthy women (P=0.0026 between groups). Diabetic women with no or very mild retinopathy had lower macular capillary blood flow velocities than those with more severe retinopathy (P=0.0164), but higher velocities than healthy women (P=0.0167). An increase temporally from the first trimester to the postpartum period was observed in diabetic women (P=0.0294) but not in healthy (P=0.2449) women. CONCLUSIONS: According to our study macular capillary blood flow velocity is higher in diabetic than in healthy women during pregnancy and the postpartum period. Further, capillary blood flow velocity seems to depend on the grade of retinopathy in pregnant diabetic women. These data support the concept that capillary hyperperfusion may play a role in the development of diabetic retinopathy during pregnancy.

Adult↗
PubMed2002

Treatment of deep venous thrombosis with low-molecular-weight heparin during pregnancy.

Low-molecular-weight (LMW) heparins have been shown to be at least as effective as unfractionated (UF) heparin in the treatment of deep venous thrombosis (DVT) in nonpregnant subjects. LMW heparins have been shown to be safe when used during pregnancy as they do not cross the placenta. Up to now, they have been used mainly in thromboprophylaxis during pregnancy and rarely in the treatment of acute DVT in pregnant women. In a prospective observational study, we compared the effectiveness and safety of the LMW heparin, dalteparin, with UF heparin in the initial treatment (first week) of DVT during pregnancy. After confirmation of DVT by ultrasonography, 10 women were treated with UF heparin (25,430 IU/day, mean) and 21 women with dalteparin (16,000 IU/day, mean) for 7 days and, thereafter, all women were given treatment doses of LMW heparin for another 2 weeks. The dose was then gradually decreased and kept at a high prophylactic dose until delivery. One patient in the dalteparin group had recurrence of DVT 2 weeks after starting the treatment. No differences were observed between the groups in symptoms or bleeding complications during pregnancy and delivery. Our results indicate that LMW heparin is as effective and safe as UF heparin for the first week of treatment, but LMW heparin has the advantage of being easily administered and few laboratory controls are required.

Adult↗
PubMed2002

Enzyme-inducing antiepileptic drugs in pregnancy and the risk of bleeding in the neonate.

BACKGROUND: Case reports suggest that maternal hepatic enzyme-inducing antiepileptic drugs (AED) increase the risk for neonatal bleeding. Antenatal administration of vitamin K(1) to mothers using these drugs therefore is widely recommended. There are, however, no studies on the incidence of this complication. OBJECTIVE: To assess the occurrence of bleeding complications in newborns exposed to maternal enzyme-inducing AED in utero. METHODS: The authors prospectively followed 662 pregnancies in women with epilepsy who used enzyme-inducing AED. Of the 667 neonates, 463 were exposed to carbamazepine, 212 to phenytoin, 44 to phenobarbital, 11 to primidone, and 7 to oxcarbazepine. The control subjects were 1,324 nonepileptic pregnancies (1,334 neonates) matched for maternal age, parity, number of fetuses, and delivery date. None of the mothers received vitamin K(1) during pregnancy, but all infants received 1 mg vitamin K(1) intramuscularly at birth. RESULTS: A bleeding complication was observed in five (0.7%) of the offspring exposed to maternal enzyme-inducing AED and in five (0.4%) control subjects (p = 0.3). After logistic regression analysis was performed, bleeding was associated with birth at <32 weeks of gestation (adjusted OR = 13; 95% CI = 2.7 to 64) and alcohol abuse (adjusted OR = 17; 95% CI = 1.8 to 162) but not with exposure to enzyme-inducing AED (adjusted OR = 1.1; 95% CI = 0.3 to 4.6; p = 0.8). CONCLUSIONS: These data do not support the hypothesis that maternal enzyme-inducing AED increase the risk for bleeding in the offspring. Antenatal administration of vitamin K to these mothers may still be needed in selected cases.

Adult↗
PubMed2002

Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin.

Venous thromboembolism remains an important cause of maternal mortality. In a randomised open study, 44 pregnant women with confirmed previous or current thromboembolism were randomised to receive either low-molecular-weight heparin, dalteparin (N = 21) once daily subcutaneously or unfractionated sodium heparin (UF heparin, N = 23) twice daily subcutaneously for thromboprophylaxis during pregnancy and puerperium. Bone mineral density (BMD) in the lumbosacral spine was measured with dual X-ray absorptiometry (DEXA) 1, 6, 16, 52 weeks and, if possible, 3 years after delivery. BMD values were also compared with those of healthy, delivered women (N = 19). Mean BMD of the lumbar spine was significantly lower in the unfractionated heparin group compared with the dalteparin and with the control groups (repeated measures ANOVA p = 0.02). BMD in the dalteparin group did not differ from BMD of healthy delivered women. Multiple logistic regression analysis revealed that therapy was the only independent factor influencing BMD at weeks 16 and 52. Therefore we recommend use of dalteparin instead of UF heparin for long-term thromboprophylaxis during and after pregnancy.

Absorptiometry, Photon↗
PubMed2001

Reduced pain tolerance during and after pregnancy in women suffering from fear of labor.

Pain tolerance in women suffering and not suffering from fear of labor during and after pregnancy were compared. Twenty women with labor fear and 20 control women were subjected to a cold pressor test (CPT) on average 1 month before delivery and 9 months later. Half the volunteers were nulliparous and half parous. Pain endurance time (PET) and intensity of pain (Visual Analogue Scale, VAS) during CPT was assessed. Patients in the fear group tolerated CPT for a significantly shorter time than did women without fear both in pregnancy (154.8+/-109.9 s vs. 282.5+/-60.1 s (mean+/-SD), P<0.001), and in the postpartum period (128.6+/-111.7 s vs. 279.6 +/-60.3 s, P=0.002). Those with labor fear experienced CPT as significantly more painful than did the controls both during pregnancy (VAS 6.68+/-1.9 vs. 3.78+/-2.0 (mean+/-SD), P<0.001) and after (VAS 7.73+/-1.5 vs. 5.92+/-3.0, P=0.04). PET and VAS values correlated during pregnancy (r=-0.62, P<0.001), but not after pregnancy (r=-0.30, not significant). Parity was not associated with either PET or VAS scores. As a rule, pain in all women during CPT was regarded to be lower during pregnancy than after pregnancy (VAS 4.87+/-2.4 vs. 6.60+/-2.6, P=0.001). Patients with fear of labor were characterized by pain intolerance also in circumstances other than labor. This fact may indicate enhanced sensitivity to pain-causing mechanisms in women who develop fear of labor.

Adult↗