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Biomedical subjects

R Kaaja

Publications and source records attributed to R Kaaja.

At least 19 recordsLinked to original sources

Preanalytical conditions that affect coagulation testing, including hormonal status and therapy.

Preanalytical conditions, be they due to the individual's physiologic state or to exogenous factors, can affect coagulation factors, in either a transient or a persistent manner, and need to be considered in laboratory testing. These conditions include physical and mental stress, diurnal variation, hormone levels and posture at the time of blood drawing. While testing of these factors has not been exhaustive and some results are conflicting, guidelines for testing conditions can be given.

Anticoagulants↗

Pre-eclampsia but not pregnancy-induced hypertension is a risk factor for diabetic nephropathy in type 1 diabetic women.

AIMS/HYPOTHESIS: Our aim was to study whether pre-eclampsia and pregnancy-induced hypertension are predictors of diabetic nephropathy in type 1 diabetic women. MATERIALS AND METHODS: A total of 203 type 1 diabetic women, who were pregnant between 1988 and 1996 and followed at the Department of Obstetrics and Gynaecology in Helsinki, were re-assessed after an average of 11 years within the nationwide, multi-centre Finnish Diabetic Nephropathy Study. Diabetic nephropathy was defined as microalbuminuria, macroalbuminuria or end-stage renal disease. RESULTS: Patients with prior pre-eclampsia had diabetic nephropathy more often than patients with a normotensive pregnancy (diabetic nephropathy vs normal albumin excretion rate: 41.9% vs 8.9%; p<0.001), whereas patients with a history of pregnancy-induced hypertension did not (10.3% vs 8.9%; p=0.81). CHD was more prevalent in patients with a history of pre-eclampsia than in patients with a normotensive pregnancy (12.2% vs. 2.2%; p=0.03). Pre-eclampsia (odds ratio [OR] 7.7, 95% CI 1.6-36.1; p=0.01) and HbA(1c) (OR 2.0, 95% CI 1.1-3.8; p<0.05) were associated with incident diabetic nephropathy even when adjusted for follow-up time, BMI, smoking, diabetes duration and age. CONCLUSIONS/INTERPRETATION: These data suggest that a history of pre-eclamptic pregnancy but not pregnancy-induced hypertension is associated with an elevated risk of diabetic nephropathy.

Adult↗

Variations in the thrombomodulin and endothelial protein C receptor genes in couples with recurrent miscarriage.

BACKGROUND: Recurrent miscarriage (RM) has been suggested to be caused by mutations in genes coding for various coagulation factors resulting in thrombophilia. Mouse models indicate that genes involved in the protein C anticoagulant pathway are essential for normal embryonic development. Loss of function of two of these genes, thrombomodulin (TM) and endothelial protein C receptor (EPCR), causes embryonic lethality in mice. The aim of this study was to determine whether variations in the human TM or EPCR genes are associated with an increased risk for RM. METHODS: Forty-six RM patients and 191 controls were screened for mutations in TM and EPCR using denaturing high-performance liquid chromatography (DHPLC). The partners of 40 RM patients were also screened. RESULTS: One exonic and one intronic variation in TM and two exonic and two intronic sequences in EPCR were detected. Four variants were common in both patients and controls. A previously identified truncating mutation in EPCR, suggested to have a role in pregnancy complications, was identified in two patients and one control. A novel deletion in the 3'UTR region of TM was detected, but its significance remains unsolved. CONCLUSIONS: These data suggest that mutations in the TM or EPCR genes are not a major cause of RM, although they may exert a modifier effect in combination with other variants.

3' Untranslated Regions↗

Oral health in women with pregnancy and delivery complications.

Oral health was retrospectively studied in 207 women (mean age 30 years) in the Helsinki Womens' Hospital with the hypothesis that women with pregnancy complications and/or delivery complications would present poorer dental status than women without complications. Computerized dental records of the City of Helsinki Health Department were used with decayed, missing, filled index (DMF) and community periodontal index (CPI) scoring systems and a summary dental health index (DHI) was constructed for statistics. In 72%, the delivery was uncomplicated, while 18% had Caesarean section. Of the women, 8% had gestational diabetes, 7.1% had gestational hypertension, and 1.8% had preeclampsia. Fifteen (6.6%) preterm babies were born; eight (3.5%) babies weighed <2.500 g, seven (3.2%) received a 1-min Apgar point <7 indicating less than satisfactory state of the newborn. DMF was 12.9+/-6.6 in women without complications compared to 15.3+/-6.7 in women with complications (n.s.). CPI values did not differ between the groups. The mean DHI values were 2.07 in women with normal pregnancy complications and no delivery complications, 2.23 in those with pregnancy complications, and 2.13 in those with delivery complications, respectively. In logistic regression analysis, no oral health parameters associated with any complications. Thus, this study failed to show an association between poor dental health and pregnancy or delivery complications.

Adolescent↗

Pregnancy-associated recurrent liver necrosis in patient with antiphospholipid syndrome.

The presence of antiphospholipid antibodies is associated with thromboembolic events, thrombocytopenia and numerous pregnancy complications such as recurrent miscarriage, preeclampsia and HELLP syndrome. This condition is known as the antiphospholipid syndrome (APS). We describe a rare case of recurrent liver necrosis postpartum in two consecutive pregnancies of woman with systemic lupus erythematosus (SLE) and positive antiphospholipid antibodies (aPL) who underwent complete recovery.

Adult↗

Peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a rare cardiac disorder of unknown cause that occurs in pregnant females, most commonly in the early postpartum period. It shares many clinical characteristics with idiopathic dilated cardiomyopathy but occurs at a younger age and is associated with a better prognosis. The etiology and pathogenic mechanisms have been difficult to study, however current hypotheses include infectious, immunologic, nutritional, and iatrogenic causes. Diagnosis is based upon the clinical presentation of congestive heart failure and objective evidence of left ventricular systolic dysfunction. Mortality rates over the past 10 years in PPCM have decreased, most likely due to advances in medical therapy for heart failure and use of implantable defibrillators. For those patients, who remain refractory to conventional pharmacologic therapy, cardiac transplantation and mechanical circulatory support are viable options. In less than 50% of PPCM patients, left ventricular function normalizes with pharmacologic therapy. However, subsequent pregnancies are often associated with recurrence of left ventricular systolic dysfunction.

Cardiomyopathies↗

Inflammatory markers and retinopathy in pregnancies complicated with type I diabetes.

AIM: The relation of maternal cytokine levels to retinopathy progression during diabetic pregnancy is a less studied subject. Therefore, we investigated levels of systemic proinflammatory markers, C-reactive peptide (CRP), interleukin-6 (IL-6) and circulating vascular cell adhesion molecule-1 (VCAM-1) during pregnancy and postpartum in relation to the progression of diabetic retinopathy (DR). METHODS: A prospective follow-up study of 39 pregnant women with Type I diabetes and eight nondiabetic pregnant women was performed. DR was graded from fundus photographs. Plasma levels of systemic proinflammatory markers were measured by immunofluorometric assay (CRP) and by enzyme-linked immunosorbent assay (IL-6 and VCAM-1) in the first, second (diabetics only), third trimester of pregnancy, and 3 and 6 months postpartum (diabetics only). RESULTS: Our diabetic women had good glycaemic control (HbA1c 6.9 +/- 0.8). The levels of IL-6, VCAM-1, and CRP did not differ between diabetic and nondiabetic women throughout pregnancy and postpartum (repeated measures ANOVA between the groups). An association between CRP and progression of retinopathy was observed in diabetic women (P = 0.037). Additional evidence of inter-relationship could be revealed as CRP was higher in those diabetic women with worse glycaemic control (HbA1c) (P = 0.038). CONCLUSIONS: During pregnancy and postpartum, levels of proinflammatory factors (IL-6, CRP, VCAM-1) seem to be generally similar in Type I diabetic women compared to nondiabetic controls. However, CRP levels were higher in those diabetic women with progression of retinopathy and in those with worse glycaemic control.

Adult↗

Congenital anomaly rate in offspring of mothers with diabetes treated with insulin lispro during pregnancy.

AIM: To determine the rate of major congenital anomalies in offspring of a large group of women with diabetes mellitus treated with insulin lispro (Humalog). METHODS: This multinational, multicentre, retrospective study included mothers with diabetes mellitus (diagnosed prior to conception) who were treated with insulin lispro for at least 1 month before conception and during at least the first trimester of pregnancy. Anomalies were assessed by two independent dysmorphologists not affiliated with the sponsor. RESULTS: The charts of 496 women were reviewed for 533 pregnancies resulting in 542 offspring (500 live births, 31 spontaneous and seven elective abortions, and four stillbirths). Mothers' characteristics: mean (+/- SD) age was 29.9 (+/- 5.2) years, 85.6% were Caucasian and 97.2% had Type 1 diabetes mellitus. Insulin lispro continued to be the main mealtime insulin for more than 96% of the women during the second and third trimester. The dysmorphologists determined that 27 (5.4%) offspring had major congenital anomalies and 2 (0.4%) offspring had minor congenital anomalies. CONCLUSIONS: The rate of major congenital anomalies was 5.4% [95% CI (3.45%, 7.44%)] for offspring of mothers with diabetes mellitus treated with insulin lispro before and during pregnancy. The current published rates of major anomalies in infants born to mothers with diabetes treated with insulin are between 2.1 and 10.9%. This suggests that the anomaly rate with insulin lispro treatment does not differ from the published major congenital anomaly rates for other insulin treatments.

Abnormalities, Drug-Induced↗

Diurnal blood glucose profiles in women with gestational diabetes with or without hypertension.

AIM: The aim of the study was to establish whether diurnal blood glucose profiles differed in women with gestational diabetes (GDM) with different forms of hypertensive complications. METHODS: The subjects were patients diagnosed at 26-32 gestational weeks as having GDM (n = 178). They were classified as being normotensive, having chronic hypertension (with or without superimposed pre-eclampsia on chronic hypertension) or pregnancy-induced hypertension (with or without proteinuria). We compared diurnal blood glucose profiles (blood glucose taken every 4 h over 24 h) in these three groups. RESULTS: Hypertension complicated 43% of the women with GDM. The glucose profiles were similar between the three groups, except that in early morning hours (from 04:00 to 08:00 h) blood glucose concentrations increased in mothers with chronic hypertension, whereas they decreased in the normotensive women. In univariate regression analysis, both obesity (BMI > or = 28 kg/m(2)) and chronic hypertension showed significant association with blood glucose rise from 04:00 to 08:00 h, but in a multiple regression model neither showed significant independent effect. CONCLUSIONS: The rise in blood glucose levels during the early morning hours in women with GDM and chronic hypertension could reflect greater insulin resistance and sympathetic overactivity.

Adult↗

Effects of moxonidine and metoprolol in penile circulation in hypertensive men with erectile dysfunction: results of a pilot study.

Centrally acting (moxonidine) and peripherally acting (metoprolol) sympatholytic agents might have different actions upon penile circulation in hypertensive men with erectile dysfunction. A total of 11 nonsmoking, hypertensive but otherwise healthy men with erectile dysfunction were studied after 8 weeks on moxonidine monotherapy (0.4 mg per day, increased to 0.6 mg if needed) and then after 8 weeks of metoprolol monotherapy (100 mg per day, increased to 200 mg if needed) in a crossover design. At the end of each treatment phase, the subjects were asked about their subjective erectile capacity (nocturnal and coital erections), and resting and stimulated (after intracavernosal injection of a mixture of alprostadil and phentolamine) penile deep artery diameters and systolic peak velocities were measured by color Doppler ultrasonography. There were no significant differences in blood pressure after either therapy. The change from earlier antihypertensive therapy, moxonidine produced significant subjective amelioration of sexual dysfunction in 9/11 of the men (< or = 0.001), whereas 9/11 returned to impaired dysfunction after crossover to metoprolol treatment. Resting and stimulated deep penile diameters and peak systolic velocities were higher after moxonidine treatment compared with metoprolol (diameters: < or = 0.004, < or = 0.0001; velocities: < or = 0.008, < or = 0.038). The centrally acting sympatholytic agent moxonidine seems to improve erectile function both subjectively and objectively and has a better effect on penile circulation compared with the peripherally acting sympatholytic agent metoprolol.

Adult↗

Plasma exchange in severe postpartum HELLP syndrome.

We present a case of extremely severe postpartum HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, associated with activation of coagulation, massive recurrent intra-abdominal bleeding requiring two laparotomies, renal failure, and central nervous system symptoms. This case underlines the complexity of pregnancy-related thrombotic microangiopathies regarding their differential diagnosis, multiple organ dysfunction, as well as management. Systemic endothelial cell injury plays a central role in the pathogenesis of thrombotic microangiopathies. Treatment of HELLP syndrome usually consists of administration of antihypertensive therapy and magnesium sulfate. No consensus exists regarding the use of plasma exchange or corticosteroids. Plasma exchange was a major part of the treatment regime in our patient. Early plasma exchange may be considered as an adjuvant therapy in severe and progressive postpartum HELLP syndrome.

Adult↗

Increased thromboxane production in women with a history of venous thromboembolic event: effect of heparins.

We investigated the production of prostacyclin and thromboxane in pregnant women with a previous venous thromboembolic event before, during and after the use of unfractionated heparin and low molecular weight heparin (dalteparin). Twenty women were studied before starting heparin prophylaxis (before 20 weeks of gestation), during heparin prophylaxis (at 30 weeks of gestation) and after heparin prophylaxis (16 weeks after delivery). Ten pregnant women with no history of thromboembolism were studied as the control group. Urinary output of the stable metabolite of prostacyclin (2,3-dinor-6-keto-PGF1alpha) and that of thromboxane A2 (2,3-dinor-TxB2), as well as a number of markers of thrombophilia were measured and expressed as mean (+/-SEM). Women with a history of thromboembolism were characterized by normal prostacyclin production but elevated thromboxane production (44.0 +/- 4.1 versus 19.0 +/- 3.6 ng/mmol creatinine, P < 0.001) at 12 weeks of pregnancy. Heparin prophylaxis (regardless of the type) had abolished elevated thromboxane concentrations at 30 weeks of gestation. Four months after delivery, thromboxane dominance had returned (25.2 +/- 3.5 versus 13.6 +/- 2.1 ng/mmol creatinine, P < 0.01). The presence of hereditary thrombophilia (9/20) was not associated with any changes in prostanoid concentrations. Thus, women with a history of venous thromboembolic events have thromboxane dominance during and after pregnancy, but this dominance can be eliminated through the use of heparins.

6-Ketoprostaglandin F1 alpha↗

Leptin during and after preeclamptic or normal pregnancy: its relation to serum insulin and insulin sensitivity.

Hyperleptinemia may be part of the insulin resistance syndrome. We studied serum leptin in preeclampsia, which is an insulin-resistant state, and sought associations between leptin and insulin or insulin sensitivity during and after pregnancy. Twenty-two proteinuric preeclamptic women and 16 normotensive controls were studied during the third trimester. Leptin was higher in preeclampsia (mean +/- SE, 34.6 +/- 3.9 v 20.0 +/- 3.3 microg/L, P = .002) and correlated directly with the level of proteinuria (r = .47, P = .03) and normal pregnancy (r = .52, P = .04), whereas insulin sensitivity as assessed by an intravenous glucose tolerance test showed no relationship to leptin. Leptin was 19.0 +/- 3.6 microg/L in 14 preeclamptic women and 10.1 +/- 2.0 microg/L (P = .11) in 11 controls 3 months after delivery. Leptin correlated directly with insulin both in preeclamptic puerperal women (r = .63, P = .02) and in controls (r = .81, P = .003). Leptin and insulin sensitivity correlated only in preeclamptic puerperal women (r = -.59, P = .02). In conclusion, (1) serum leptin is elevated in preeclampsia, (2) insulin is an important determinant of serum leptin in preeclamptic and normotensive women both during pregnancy and in the puerperium, and (3) hyperleptinemia may be part of the insulin resistance syndrome also in women with prior preeclampsia.

Adult↗

677 C-->T polymorphism of the methylenetetrahydrofolate reductase gene and preeclampsia.

OBJECTIVE: To evaluate C to T substitution at nucleotide 677 of N(5), N(10)-methylenetetrahydrofolate reductase gene in women with prior preeclamptic or normotensive pregnancies. METHODS: Methylenetetrahydrofolate reductase genotypes were determined in 113 Finnish women with preeclamptic first pregnancies and 103 controls with one or more normotensive pregnancies, using polymerase chain reaction and restriction enzyme analysis. Preeclampsia was defined as severe in 100 women who fulfilled one or more of the subsequent criteria: systolic blood pressure (BP) at least 160 mmHg, diastolic BP at least 110 mmHg, or proteinuria at least 2 g per 24-hour urine collection. RESULTS: There were no significant differences in prevalences of the methylenetetrahydrofolate reductase genotypes (CC, CT, and TT) between groups (57%, 40%, and 3% in the preeclamptic group and 54%, 39%, and 7%, respectively, in controls). The frequency of the T677 allele was 0.23 in the preeclamptic group and 0.26 in the control group (difference 0.03; 95% confidence interval -0.08, 0.14; P =.51). Our sample had 60% power to detect a difference of the allele frequencies similar to that (0.12) reported previously. The result was similar when analysis was restricted to patients with severe preeclampsia (T677 allele frequency 0.22). CONCLUSION: A carrier status for the T677 allele of the methylenetetrahydrofolate reductase gene does not predispose to preeclampsia, at least in the Finnish population.

Adult↗

Thromboprophylaxis with low molecular weight heparin (dalteparin) in pregnancy.

Venous thromboembolism remains an important cause of maternal mortality. For women at risk during pregnancy, the recommended venous thromboembolismprophylaxis is unfractionated heparin. Low molecular weight heparins, such as dalteparin, also may be suitable, but randomised trials have not been performed. Pregnant women (105) with confirmed previous or current thromboembolism were randomised to receive either unfractionated heparin twice daily (mean 20569 IU/day) or dalteparin once daily (mean 4631 IU anti-factor Xa units/day) subcutaneously for thromboprophylaxis during pregnancy and postpartum period. Recurrence of venous thromboembolism and safety of treatments were assessed. Dalteparin administered once daily was safe and effective in thromboprophylaxis during pregnancy and postpartum.

Adult↗