Tiina Ojala

Antimicrobial activity of some coumarin containing herbal plants growing in Finland.

Antimicrobial screening against selected Gram-positive and Gram-negative bacteria, yeasts, mold, as well as plant pathogenic fungi, with emphasis on method optimization was carried out on methanol extracts prepared from seven plants grown in Finland. Sensitivity to the extracts was found to vary considerably among the micro-organisms, the extract from Petroselinum crispum and Ruta graveolens showing the highest toxicity against Rhizoctonia solani. The growth of Heterobasidium annosum was inhibited, whereas that of Phytophtora (cactorum) was promoted by all the extracts. The antibacterial and antifungal activities of six natural coumarin compounds were weak, except for the inhibitory effect against Fusarium culmorum.

Impact of maternal diet during pregnancy and breastfeeding on infant metabolic programming: a prospective randomized controlled study

Objectives:To evaluate the impact of maternal diet and intensive dietary counselling during pregnancy and breastfeeding on the infants metabolic status.Subjects/Methods:At the first trimester of pregnancy, 256 women were randomized into a control/placebo group and two dietary counselling groups (diet/probiotics and diet/placebo). The counselling, with double-blind randomization to probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis) or placebo, targeted excessive saturated fat and low fibre consumption. Maternal diet was evaluated repeatedly during pregnancy and postpartum by means of 3 days’ food diaries. Metabolic markers, serum 32–33 split and intact proinsulin, leptin/adiponectin ratio, skinfold thickness and waist circumference were measured of 194 healthy infants at the age of 6 months, and the high levels were taken to mirror adverse metabolic status.Results:The proportion of infants with a high 32–33 split proinsulin was significantly lower in dietary counselling with probiotics (n=6/62, 9.7%) or placebo (n=7/69, 10.1%) compared with the control/placebo group (n=17/63, 27.0%). The high split proinsulin was associated with larger skinfold thickness, waist circumference and higher leptin/adiponectin ratio in the infants (P<0.05). With respect to maternal diet during pregnancy, the highest and lowest tertiles of fat intake increased the infant’s risk of high split proinsulin, whereas those of butter associated correspondingly with the infants waist circumference. Further, breastfed infants showed a reduced risk of high split proinsulin and leptin/adiponectin ratio compared with formula-fed infants.Conclusions:Modification of maternal diet during pregnancy and breastfeeding may benefit infant metabolic health. High split proinsulin reflects adverse metabolic status in infancy, which can be improved by early dietary counselling.

New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies

Background:We report a new mutation in the human DNAJC19 gene that causes early onset dilated cardiomyopathy syndrome (DCMA).Methods:Two brothers of Finnish origin presented with an unusual combination of early onset dilated cardiomyopathy syndrome, a disease which was associated with cardiac noncompaction, microcytic anemia, ataxia, male genital anomalies and methylglutaconic aciduria type V. Suspicion of a DCMA syndrome prompted sequencing of the human DNAJC19 gene.Results:Sequencing of the human DNAJC19 gene showed a homozygous single nucleotide (A) deletion in alanine 63 coding triplet in exon 6, which does not immediately cause amino acid change but leads 11 amino acids later to a stop codon and to premature termination of the peptide. This DNAJC19 protein is located in the inner mitochondrial membrane and has been shown to function as a mitochondrial chaperone.Conclusion:This is the first clinical report of DCMA syndrome, a human DNAJC19 deficiency, that is related to cases of severe dilated cardiomyopathy diagnosed in Europe. DNAJC19 deficiency causes a relatively specific finding in urinary organic acid analysis (methylglutaconic aciduria type V), which together with the clinical features of the ensuing cardiac disease, allows for effective screening before undertaking molecular genetic analysis.

Excellent functional result in children after correction of anomalous origin of left coronary artery from the pulmonary artery – a population-based complete follow-up study☆

Surgical strategy to construct a two-coronary system for a patient with anomalous origin of left coronary artery from pulmonary artery (ALCAPA) has evolved with time. Limited long-term follow-up data are available on these children. We report population-based follow-up in children operated on for ALCAPA. In total, 29 patients underwent aortic reimplantation of ALCAPA between 1979 and 2006. Twenty (69%) children were repaired with direct aortic implantation, five (17%) with a modified tubular extension technique, and four (14%) patients with an intrapulmonary baffling technique. Early postoperative mortality (<30 days) was 17%. No late mortality (>30 days) was detected. The median length of follow-up was 11 years (range 10 months-27 years). Global left ventricular function by echocardiography (M-mode) was within normal limits (>30%) in all patients one year after operation. Functionally, 80% of patients were classified in NYHA class I, 20% in NYHA II, and 0% in NYHA classes III/IV at the time of the last examination. Excellent results with good long-term outcome can be achieved in infants with ALCAPA using reimplantation techniques. Normalization of cardiac function is expected within the first year in all operative survivors with a patent coronary system.

Nordic pulse oximetry screening – implementation status and proposal for uniform guidelines

Pulse oximetry screening of newborn infants increases early detection of critical congenital heart disease and minimises the risk of circulatory collapse before surgery. This study provides an update on the implementation of pulse oximetry screening in the Nordic countries and proposes standardised guidelines.

Radiotherapy‐related arterial intima thickening and plaque formation in childhood cancer survivors detected with very‐high resolution ultrasound during young adulthood

The aim of the study was to evaluate arterial morphology and function in a national cohort of long‐term survivors of high‐risk neuroblastoma (NBL) treated with high‐dose chemotherapy and autologous hematopoietic stem cell transplantation with or without total body irradiation (TBI).

Fetal cardiac sympathetic activation is linked with maternal body mass index

BACKGROUND Sympathetic over activity has been suggested to impact on the risk of cardiovascular diseases. The origin of abnormalities in the autonomic nervous system is unknown, but it is susceptible to environmental influences during the critical periods of human development. AIMS To examine the influence of maternal characteristics on fetal cardiac autonomic nervous activation. STUDY DESIGN Prospective, observational study. SUBJECTS 41 fetuses from normal pregnancy born after 36 gestational weeks. OUTCOME MEASURES Maternal characteristics that affect fetal intrauterine well-being intrauterine environmental factors were evaluated, including pre-pregnancy body mass index as well as GHbA1c, blood pressure and 3-day food diaries from each trimester of pregnancy. To assess intrapartum fetal cardiac sympathovagal activation fetal ECG was recorded for 1 h during delivery. Heart rate variability was measured using power spectrum analysis of low-to-high frequency ratio of fetal heart rate variability. RESULTS Cardiac sympathetic activation measured during delivery was associated with maternal pre-pregnancy body mass index (r=0.33, p=0.03), placental weight (r=0.4, p=0.008) and the immaturity of the fetus (r=-0.3, pb0.05). CONCLUSION Early intrauterine environmental factors such as maternal pre-pregnancy body mass index are associated with fetal sympathetic activation with a potential for cardiovascular programming.

Do spectral bands of fetal heart rate variability associate with concomitant fetal scalp pH

BACKGROUND Objective information on specific fetal heart rate (FHR) parameters would be advantageous when assessing fetal responses to hypoxia. Small, visually undetectable changes in FHR variability can be quantified by power spectral analysis of FHR variability. AIMS To investigate the effect of intrapartum hypoxia and acidemia on spectral powers of FHR variability. STUDY DESIGN This is a retrospective observational clinical study with data from an EU multicenter project. SUBJECTS We had 462 fetuses with a normal pH-value (pH>7.20; controls) in fetal scalp blood sample (FBS) and 81 fetuses with a low scalp pH-value (≤ 7.20; low-FBS pH-fetuses). The low-FBS pH-fetuses were further divided into two subgroups according to the degree of acidemia: fetuses with FBS pH7.11-7.20 (n = 58) and fetuses with FBS pH ≤7.10 (n = 23). OUTCOME MEASURES Spectral powers of FHR variability in relation to the concomitant FBS pH-value. RESULTS Fetuses with FBS pH ≤7.20 had increased spectral powers of FHR variability compared with controls (2.49 AU vs. 2.23 AU; p = 0.038). However, the subgroup of most affected fetuses (those with FBS pH ≤7.10) had significantly lower FHR variability spectral powers when compared to fetuses with FBS pH7.11-7.20. CONCLUSIONS This study shows that spectral powers of FHR variability change as a fetus becomes hypoxic, and that spectral powers decrease with deepening fetal acidemia.

Prenatal Diagnosis Improves the Postnatal Cardiac Function in a Population-Based Cohort of Infants with Hypoplastic Left Heart Syndrome

BACKGROUND Prenatal diagnosis of hypoplastic left heart syndrome (HLHS) enables planning of perinatal care and is known to be associated with more stable preoperative hemodynamics. The impact on postnatal myocardial function is poorly known. The aim of this study was to determine the impact of prenatal diagnosis of HLHS on postnatal myocardial function. METHODS A consecutively encountered cohort of 66 infants with HLHS born between 2003 and 2010 in Finland was retrospectively reviewed. Twenty-five infants had prenatal diagnoses. Postnatal global and segmental right ventricular fractional area change, strain rate, and myocardial velocity were analyzed from the apical four-chamber view using Velocity Vector Imaging. Preoperative hemodynamic status and end-organ damage measurements were the lowest arterial pH, highest lactate, alanine aminotransferase, and creatinine. Early mortality was studied until 30 days after Norwood procedure. RESULTS Prenatally diagnosed infants had better cardiac function (fractional area change, 27.9 ± 7.4% vs 21.1 ± 6.3%, P = .0004; strain rate, 1.1 ± 0.6/1.3 ± 1.0 vs 0.7 ± 0.2/0.7 ± 0.3 1/sec, P = .004/.003; myocardial velocity, 1.6 ± 0.6/2.0 ± 1.1 vs 1.3 ± 0.4/1.4 ± 0.4 cm/sec, P = .0035/.0009). Mechanical dyssynchrony was similar in both groups (P > .30). Infants diagnosed prenatally had less acidosis (pH = 7.30 vs 7.25, P = .005) and end-organ dysfunction (alanine aminotransferase, 33 ± 38 vs 139 ± 174 U/L, P = .0001; creatinine, 78 ± 18 vs 81 ± 44 mmol/L, P = .05). No deaths occurred among the prenatally diagnosed infants, but four deaths were recorded among postnatally diagnosed infants (P = .15). CONCLUSIONS A prenatal diagnosis of HLHS is associated with improved postnatal right ventricular function, reduced metabolic acidosis, and end-organ dysfunction.

Fetal left ventricular noncompaction cardiomyopathy and fatal outcome due to complete deficiency of mitochondrial trifunctional protein

AbstractWe report a fetal case with fatal outcome having a novel mutation in the HADHB gene, coding the beta-subunit of the mitochondrial trifunctional protein. Parents had a previous pregnancy loss due to fetal heart failure and hydrops. The next pregnancy led to left ventricular noncompaction and increasing pleural effusions after 29 gestational weeks. The fetus was small for gestational age, and long bones were abnormally short. The baby was born severely asphyxiated at 32 gestational weeks by cesarean section. Intensive care was withdrawn due to failure to thrive and suspicion of a severe mitochondrial disorder. Postmortem brain MRI suggested microcephaly with a simplified gyral pattern. The lateral cerebral ventricles were normal. Chromosome analysis was normal (46, XX). Fibroblasts cultured from a skin biopsy of the baby revealed the large homozygous deletion c.1109+243_1438-703del in the HADHB gene, and heterozygous mutations were detected in both parents. The deletion has not been reported earlier. Conclusion: It is important to differentiate systemic metabolic diseases from disorders that affect only the cardiac muscle. Trifunctional protein deficiency is a relatively rare disorder of the fatty acid β-oxidation cycle. The mutation in the HADHB gene causes a systemic disease with early-onset cardiomyopathy. Understanding the molecular genetic defect of the patient allows appropriate genetic counseling of the family.What is Known:• Mitochondrial disorders as a group are an important etiology for fetal cardiomyopathies including human trifunctional protein (TFP) disorders and several other mitochondrial diseases.What is New:• We report a fetal case with fatal outcome having a novel mitochondrial trifunctional protein mutation (c.1109+243_1438-703del in the HADHB gene).