Jacek J. Pietrzyk

Extracorporeal life support in severe propranolol and verapamil intoxication.

Combined poisoning with calcium-channel blockers and β-blockers is usually associated with severe heart failure. This report shows the effectiveness of emergency extracorporeal life support in treating life-threatening simultaneous propranolol and verapamil intoxication. A 15-year-old girl presented in cardiogenic shock after alcohol consumption and a propranolol and verapamil overdose; plasma concentrations: propranolol, 0.53 m/mL; verapamil, 1.06 mg/mL. She was successfully resuscitated with extracorporeal life support. Therapeutic plasma exchange was initiated. Extracorporeal support was discontinued 70 hours later. The patient made a full recovery. Simultaneous verapamil and propranolol overdoses can cause severe hemodynamic compromise and arrest of electrical and mechanical function of the heart. Emergency extracorporeal life support can successfully maintain vital organ blood flow and allows time for drug metabolism, redistribution, and removal. Therapeutic plasma exchange may reduce the time of emergency extracorporeal life support. Emergency extracorporeal life support should be considered early in cases of near-fatal intoxications with cardiodepressive drugs.

Preterm birth and respiratory disease in later life

Chronic respiratory diseases are a common complication of preterm birth, particularly among very immature infants or those suffering from bronchopulmonary dysplasia. Major progress in the treatment of preterm newborns has changed the pattern of late respiratory complications. The major respiratory problem in infancy and early childhood is respiratory exacerbations caused by infections (particularly viral ones), which need hospitalization. The symptoms become mild in school-age children; however, a group of children still present with chronic airway obstruction defined by recurrent episodes of wheezing and decreased lung function tests (decreased forced expiratory volume). For some preterm infants, particularly those with bronchopulmonary dysplasia, obstructive lung disease persists into adulthood. They are very likely to develop chronic obstructive pulmonary disease or similar disease later in life. In these patients, a program of lung function monitoring and pulmonary prophylaxis by means of elimination of specific risk factors in adulthood is advisable.

Genetic risk factors of bronchopulmonary dysplasia.

The aim of the study was to assess the association between bronchopulmonary dysplasia (BPD) and polymorphisms of genes coding for vascular endothelial growth factor (VEGF), transforming growth factor (TGF-β1), insulin-like growth factor (IGF-1), and 5,10-methylenetetrahydrofolate reductase (MTHFR). A sample of 181 newborns with mean gestational age of 28 wk was prospectively evaluated. Molecular analysis of TGF-β1 −800G>A, −509C>T, 10T>C, 25G>C, VEGF −460T>C and 405G>C and MTHFR 677C>T polymorphisms were performed and the number of CA repeats in the promoter region of IGF-1 gene was assessed. The frequency of all TGF-β1, IGF-1, and MTHFR polymorphisms, as well as the frequency of VEGF 405G>C polymorphism was similar in all groups. The newborns with −460TT and −460CT genotypes were significantly overrepresented in the BPD groups compared with the no BPD group. Multivariate analysis revealed that carrying T allele increased the risk of BPD by 9% (95%CI: 2–14%) above the baseline risk established for given gestational age, length of oxygen therapy, and sex. Based on our data from a single center, we propose that VEGF −460T>C polymorphism may influence the risk of BPD.

Trisomy 8 Mosaicism Syndrome Two Cases Demonstrating Variability in Phenotype

The paper presents clinical manifestations and results of cytogenetic examination of two patients with trisomy 8 mosaicism syndrome. The findings confirm the extreme phenotype variability of this syndrome. Both the first patient, a mentally retarded child with multiple dysmorphic changes, and the second, a 31-year-old woman with normal IQ and hypogammaglobulinemia as a predominant sign, revealed osteoarticular anomalies. Dermatoglyphic studies in both patients were typical for trisomy 8, and correlated with deep skin furrows. The chromosomal analysis was based on two types of lymphocyte cultures: 3-day and 2-day. A decreased percentage of trisomic cells in 3-day cultures in comparison to 2-day cultures may suggest the influence of environmental factors on spontaneous elimination of trisomic cells in vitro.

Plasma levels of leptin and soluble leptin receptor and polymorphisms of leptin gene -18G > A and leptin receptor genes K109R and Q223R, in survivors of childhood acute lymphoblastic leukemia

BackgroundApproximately 20% of children and adolescents in Europe are overweight. Survivors of pediatric acute lymphoblastic leukemia (ALL) are at increased risk of overweight and obesity. The purpose of this study was to assess leptin and leptin soluble receptor levels, as well as polymorphisms of selected genes in survivors of pediatric ALL, and the influence of chemo- and radiotherapy on development of overweight in the context of leptin regulation.MethodsEighty two patients (55% males), of median age 13.2 years (m: 4.8 years; M: 26.2 years) were included in the study. The ALL therapy was conducted according to modified Berlin-Frankfurt-Munster (BFM; n = 69) regimen or New York (n = 13) regimen. In 38% of patients cranial radiotherapy (CRT) was used in median dose of 18.2Gy (m: 14Gy; M: 24Gy). Median age at diagnosis was 4.5 (m: 1 year; M: 16.9 years) and median time from completion of ALL treatment was 3.2 years (m: 0.5 year; M: 4.3 years). Patients with BMI ≥85 percentile were classified as overweight. Correlation of plasma levels of leptin and leptin soluble receptor, and polymorphisms of leptin gene -18G > A, leptin receptor genes K109R and Q223R, and the overweight status were analyzed in relation to gender, intensity of chemotherapy (high intensity vs. standard intensity regimens) and to the use of CRT.ResultsSignificant differences of leptin levels in patients treated with and without CRT, both in the entire study group (22.2+/- 3.13 ng/ml vs. 14.9+/-1.6 ng/ml; p < 0.03) and in female patients (29.9+/-4.86 ng/ml vs. 16.9+/-2.44 ng/ml; p = 0.014), were found. Significant increase of leptin levels was also found in overweight patients compared to the non-overweight patients in the entire study group (29.2+/-2.86 ng/ml vs. 12.6+/-1.51 ng/ml; p < 0.0001), female patients (35.4+/-6.48 ng/ml vs. 18.4+/-2.5 ng/ml; p = 0.005), and male patients (25.7+/-2.37 ng/ml vs. 6.9+/-0.95 ng/ml; p < 0.0001). Negative correlation was observed for plasma levels of soluble leptin receptor and overweight status, with significant differences in overweight and non-overweight patients, both in the entire study group (18.2+/-0.75 ng/ml vs. 20.98+/-0.67 ng/ml; p = 0.017) and in male patients (18.2+/-1.03 ng/ml vs. 21.8+/- 1.11 ng/ml; p = 0.038). Significant (p < 0.05) negative correlation was found between leptin and leptin receptor levels in the entire group (correlation coefficient: 0.393) and in both gender subgroups (correlation coefficient in female patients: -0.427; in male patients: -0.396).ConclusionsThe prevalence of overweight in our cohort was higher than in general European population (31% vs 20%) and increased regardless of the use of CRT. Leptin and leptin receptor levels may be used as useful markers of high risk of becoming overweight in ALL survivors, particularly in females treated with CRT. Polymorphisms of leptin gene -18G > A and leptin receptor genes K109R and Q223R were not associated with overweight status in ALL survivors.

Gene Expression Profiling in Preterm Infants: New Aspects of Bronchopulmonary Dysplasia Development

Rationale Bronchopulmonary dysplasia is one of the most serious complications observed in premature infants. Thanks to microarray technique, expression of nearly all human genes can be reliably evaluated. Objective To compare whole genome expression in the first month of life in groups of infants with and without bronchopulmonary dysplasia. Methods 111 newborns were included in the study. The mean birth weight was 1029g (SD:290), and the mean gestational age was 27.8 weeks (SD:2.5). Blood samples were drawn from the study participants on the 5th, 14th and 28th day of life. The mRNA samples were evaluated for gene expression with the use of GeneChip® Human Gene 1.0 ST microarrays. The infants were divided into two groups: bronchopulmonary dysplasia (n=68) and control (n=43). Results Overall 2086 genes were differentially expressed on the day 5, only 324 on the day 14 and 3498 on the day 28. Based on pathway enrichment analysis we found that the cell cycle pathway was up-regulated in the bronchopulmonary dysplasia group. The activation of this pathway does not seem to be related with the maturity of the infant. Four pathways related to inflammatory response were continuously on the 5th, 14th and 28th day of life down-regulated in the bronchopulmonary dysplasia group. However, the expression of genes depended on both factors: immaturity and disease severity. The most significantly down-regulated pathway was the T cell receptor signaling pathway. Conclusion The results of the whole genome expression study revealed alteration of the expression of nearly 10% of the genome in bronchopulmonary dysplasia patients.

Automatic planning of treatment of infants with respiratory failure through rough set modeling

We discuss an application of rough set tools for modeling networks of classifiers induced from data and ontology of concepts delivered by experts. Such networks allow us to develop strategies for automated planning of a treatment of infants with respiratory illness. We report results of experiments with the networks of classifiers used in automated planning of the treatment of newborn infants with respiratory failure. The reported experiments were performed on medical data obtained from the Neonatal Intensive Care Unit in the Department of Pediatrics, Collegium Medicum, Jagiellonian University.

Can Early Echocardiographic Findings Predict Patent Ductus Arteriosus

Background: Prophylactic treatment with prostaglandin synthetase inhibitors (PSI) is potentially harmful. Moreover, long-term benefits of prophylactic use of indomethacin or ibuprofen are not proven. Early treatment of a high-risk population is alternative to the routine prophylactic use of PSI, but it remains unclear which newborn is at greatest risk for patent ductus arteriosus (PDA). Objective: Evaluation of the prognostic value of early echocardiographic studies with respect to PDA in later life. Methods: Sixty preterm infants with a mean birth weight of 1,087 g and mean gestational age of 28.5 weeks were included in a prospective study. Cardiac scans were performed in all newborns on entry into the study (within 12–48 h after birth) and further in case of clinical suspicion of PDA or obligatorily on the 7th and 28th days of life. There was no prophylactic or treatment use of any PSI during the study period. Newborns were divided into 2 cohorts: with significant left to right shunt requiring surgical ligation of PDA (n = 16) or without significant PDA during follow-up (control group, n = 44). Results: On entry, the mean internal diameter of the ductus arteriosus (2.6 vs. 0.91 mm/kg; p < 0.01), mean cardiac index across aortic valve (2.96 vs. 2.37 l/min/m2; p < 0.01) and early filling peak velocity (43.1 vs. 33.7; p = 0.01) were significantly higher in babies who later needed surgical ligation of PDA. There was no difference in the mean values of the other echocardiographic parameters studied. An early ductal diameter of >1.5 mm/kg predicted symptomatic PDA with a sensitivity of 94% and a specificity of 73%, and its positive predictive value equaled 57% and negative predictive value amounted to 97%. Conclusions: Early echocardiographic studies possess negative predictive value and may decrease unnecessary surgical ligation of PDA in very low birth weight infants.

Routine use of CANTAB system for detection of neuropsychological deficits in patients with PKU

Several studies have reported neuropsychological deficits related to hyper phenylalaninemia in patients with phenylketonuria (PKU). As computerized neuropsychological tests seem to be promising in the detection of such abnormalities, we aimed to assess the usefulness of routine use of CANTAB system in PKU clinic. A group of 49 PKU patients aged >16 years were tested by means of computerized CANTAB tests measuring speed of response, response inhibition, sustained attention, and working memory capacity. The scores achieved by study participants were analyzed with respect to their blood phenylalanine concentrations. Proper dietary control was observed in 22 patients, whereas in the remaining 27 persons, blood phenylalanine concentrations exceeded the recommended range. The results of the tests assessing sustained attention, working memory, and inhibitory control achieved by the non-compliant patients were significantly worse in comparison with patients maintaining proper diet. However, the mean scores achieved by treatment-adherent patients were also worse than expected, what could probably be related to problems with early start of treatment during their infancy. Our results confirmed the presence of specific neuropsychological deficits related to hyperphenylalaninemia in adults and adolescents with PKU. In our opinion, routine use of computerized neuropsychological tests should be recommended in PKU clinics.

Additional genetic risk factor for death in children with acute lymphoblastic leukemia: A common polymorphism of the MTHFR gene

The presence of metabolically important genetic polymorphisms may affect treatment efficacy in patients with malignancies. The objective of this prospective multicenter study was to evaluate the role of selected polymorphisms of genes associated with metabolism of chemotherapeutic drugs as prognostic markers in children with acute lymphoblastic leukemia.