János Sándor

Brain Injury Biomarkers May Improve the Predictive Power of the IMPACT Outcome Calculator

Outcome prediction following severe traumatic brain injury (sTBI) is a widely investigated field of research. A major breakthrough is represented by the IMPACT prognostic calculator based on admission data of more than 8500 patients. A growing body of scientific evidence has shown that clinically meaningful biomarkers, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), and αII-spectrin breakdown product (SBDP145), could also contribute to outcome prediction. The present study was initiated to assess whether the addition of biomarkers to the IMPACT prognostic calculator could improve its predictive power. Forty-five sTBI patients (GCS score≤8) from four different sites were investigated. We utilized the core model of the IMPACT calculator (age, GCS motor score, and reaction of pupils), and measured the level of GFAP, UCH-L1, and SBDP145 in serum and cerebrospinal fluid (CSF). The forecast and actual 6-month outcomes were compared by logistic regression analysis. The results of the core model itself, as well as serum values of GFAP and CSF levels of SBDP145, showed a significant correlation with the 6-month mortality using a univariate analysis. In the core model, the Nagelkerke R(2) value was 0.214. With multivariate analysis we were able to increase this predictive power with one additional biomarker (GFAP in CSF) to R(2)=0.476, while the application of three biomarker levels (GFAP in CSF, GFAP in serum, and SBDP145 in CSF) increased the Nagelkerke R(2) to 0.700. Our preliminary results underline the importance of biomarkers in outcome prediction, and encourage further investigation to expand the predictive power of contemporary outcome calculators and prognostic models in TBI.

Vitamin D insufficiency in a large MCTD population

OBJECTIVES The aim of the present study was to evaluate the vitamin D status in patients with mixed connective tissue disease (MCTD) and to determine which clinical symptoms, laboratory parameters and endothelial cell markers are associated with low vitamin D levels. METHODS 125 female MCTD patients and 48 age- and sex-matched healthy controls were enrolled in the study. The clinical symptoms, autoantibodies (anti-U1-RNP, anti-cardiolipin - anti-CL and anti-endothelial cell antibody - AECA), serum cytokines (IFN-γ, IL-6, IL-12, IL-23, IL-17 and IL-10), soluble endothelial cell markers (endothelin, thrombomodulin - TM, and von Willebrand factor antigen - vWFAg) and serum lipids (total cholesterol, triglyceride, LDL-C, HDL-C, apolipoprotein A1, and apolipoprotein B) were investigated for an association with vitamin D levels by univariate and multivariate statistical analyses. RESULTS The mean vitamin D levels were significantly lower in MCTD patients, as compared with the control group (26.16±13.50ng/ml vs. 34.92±9.64ng/ml; p<0.001). In laboratory parameters, vitamin D levels were inversely associated with serum IL-6 (p<0.001), IL-23 (p=0.011), IL-10 (p=0.033) cytokine levels, TM (p=0.001) and endothelin (p=0.033) levels. Low vitamin D levels were also significantly associated with carotid artery intima media thickness (p<0.001), fibrinogen (p=0.010), total cholesterol (p=0.042) and ApoA1 (p=0.004) levels. Among the clinical symptoms, the cardiovascular involvement showed an inverse correlation with vitamin D status in MCTD (p<0.001). CONCLUSIONS The prevalence of vitamin D insufficiency is high in patients with MCTD. We assume that vitamin D insufficiency along with inflammatory parameters and lipid abnormalities may provoke cardiovascular events.

Male reproductive tract abnormalities: more common after assisted reproduction?

BACKGROUND In this era of increased use of assisted reproduction (AR) techniques, the prevalence rates of hypospadias, cryptorchidism, poor semen quality have been increasing in parallel with a rising incidence of testicular cancer. It is suggested that these problems result from the disruption of gonadal development during fetal life causing the testicular dysgenesis syndrome (TDS). AIM The aim of our study was to evaluate the influence of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), on the development of male genital tract abnormalities. STUDY DESIGN AND SUBJECTS We analyzed a cohort of 15,206 neonates born from January 1, 1999 through December 31, 2008 at the Department of Obstetrics and Gynecology, Medical School, University of Pécs, including 890 children (5.9%) born after IVF or ICSI. We examined the association between these AR methods and developmental abnormalities of the genital tract (hypospadias, cryptorchidism), after controlling for potential confounding factors, such as prematurity, low birthweight and twinning. RESULTS Preterm birth and low birthweight are risk factors for hypospadias and cryptorchidism (p<0.001), twinning increases the risk of hypospadias (p<0.001). ICSI was revealed as a risk factor for hypospadias in singletons (OR: 3.190, 95%CI: 1.266-8.042) and in normal birthweight (>2500 g) infants (OR: 3.966, 95%CI: 1.193-13.181, respectively). Similar but not nonsignificant trends were seen for cryptorchidism. CONCLUSION IVF and ICSI, by increasing the risks of prematurity, low birthweight, and multiple gestation, are indirect risk factors for developing male genital malformations. In infants with normal birhtweight or from singleton pregnancies, ICSI is a specific risk factor for hypospadias.

Disconnection Mechanism and Regional Cortical Atrophy Contribute to Impaired Processing of Facial Expressions and Theory of Mind in Multiple Sclerosis: A Structural MRI Study

Successful socialization requires the ability of understanding of others’ mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

Gender differences in antidepressant use-related seasonality change in suicide mortality in Hungary, 1998-2006

Abstract Objectives. Studies show that the seasonality of suicide (spring/early summer peak, winter low) is mainly the consequence of the seasonal incidence of depression-related suicides. The aim of the present study was to analyse the relationship between increasing antidepressant utilization and national suicide rate of Hungary between 1998 and 2006, with particular regard to seasonal patterns and gender differences. Methods. Time trend analysis (ARIMA) had been applied to investigate the correlation between the trend of antidepressant prescription and both of suicide rates and seasonality index. Results. During the 9 years of the study period there was a significant (P<0.001) correlation between the steadily increasing antidepressant prescription (113%) and continuous decline in total national suicide rate (23%) as well as both in females and males (21 and 23%, respectively), but this relationship was 8-fold stronger in males. Increasing antidepressant utilization was associated with significantly decreased seasonality of suicides only among males. Conclusions. The results suggest that decreasing seasonality of suicides could be a good marker of lowering rate of depression-related suicides in the population particularly among males.

Prevalence of metabolic syndrome among Roma: A comparative health examination survey in Hungary

OBJECTIVES The objective of our study was to compare the health status of the Roma people with that of the general population in Hungary. METHODS A health examination survey to define the prevalence of metabolic syndrome and its components was performed in a representative random sample (n = 646) of the Roma population aged 20-64 years living in segregated colonies, and data were compared with that obtained in a representative random sample (n = 1819) of the Hungarian population. RESULTS The risks for central obesity, hypertension and raised triglyceride level among Roma adults were not different from the Hungarian references, while raised fasting plasma glucose or known type 2 diabetes mellitus (OR = 2.65, 95%CI 1.90-3.69), reduced HDL cholesterol level or treated lipid disorder (OR = 2.15, 95%CI 1.65-2.79) were significantly more frequent in all age groups in the Roma sample. The prevalence of metabolic syndrome (OR = 1.37, 95%CI 1.03-1.83) was also significantly higher among Roma than in the general Hungarian population. CONCLUSIONS Besides tackling the socio-economic determinants of the poor health of Roma people, specific public health interventions considering increased genetic susceptibility to metabolic disturbances are needed to improve their health status.

Arsenic in drinking water and congenital heart anomalies in Hungary.

Inorganic arsenic can get easily through the placenta however there are very few human data on congenital anomalies related to arsenic exposure. Objective of our study was to explore the associations between arsenic content of drinking water and prevalence of some congenital anomalies. Four anomalies reported to the Hungarian Congenital Anomalies Registry between 1987 and 2003 were chosen to be analysed in relation to arsenic exposure: congenital anomalies of the circulatory system (n=9734) were considered as cases, while Down syndrome, club foot and multiple congenital malformations were used as controls (n=5880). Arsenic exposure of the mothers during pregnancy was estimated by using archive measurement data for each year and for each settlement where the mothers lived. Analysis of the associations between the prevalence of congenital heart anomalies and arsenic exposure during pregnancy was performed by logistic regression. The childs gender and age of the mother were adjusted for. The associations were evaluated by using the present EU health limit value of 10.0 μg/L arsenic concentration as a cut-off point. Regular consumption of drinking water with arsenic concentration above 10 μg/L during pregnancy was associated with an increased risk of congenital heart anomalies in general (adjusted OR=1.41; 95% C.I.: 1.28-1.56), and especially that of ductus Botalli persistens (adjusted OR=1.81, 95%C.I.: 1.54-2.11) and atrial septal defect (adjusted OR=1.79; 95%C.I.: 1.59-2.01). The presented results showed an increased risk of congenital heart anomalies among infants whose mothers were exposed to drinking water with arsenic content above 10 μg/L during pregnancy. Further studies of possible similar effects of concentrations below 10 μg/L are warranted.

General practitioners' cluster: A model to reorient primary health care to public health services

ARTICLE ARTICLE ‘Why a renewal of primary health care (PHC), and why now, more than ever?’ is the question by which the World Health Report 2008 is introduced.1 A primary care system in which health professionals are just simply entry points into the health system can respond neither to the challenges of a changing world nor to the growing expectations of people for better performance. The question of how to renew PHC is answered in the Report by ‘putting people first’, that is, by visioning a people-centred PHC service ‘delivered by teams that focus on health needs, create enduring personal relationships, take responsibility for the health of all in the community along the life cycle, as well as for tackling determinants of ill-health, and in which people are partners in managing their own health and that of their community’. The vision has remained a vision until now,2 and it will remain a vision forever if its implementation is considered just a health care system reform. A definitive link between PHC and public health services has to be formed to transform the vision into reality, in line with the Health 2020,3 the new World Health Organization European health policy framework and strategy, which indicates as one of its four priority areas ‘the strengthening of people-centred health systems along with public health capacity’. Lacking preventive services is one of the many previously identified anomalies of the Hungarian primary care system that needs to be corrected.4 Primary care presently is provided by one general practitioner (GP) and one nurse per practice, assisted by an …

Transcranial Doppler-determined pulsatility index in the evaluation of endoscopic third ventriculostomy (preliminary data).

Objective. Endoscopic 3rd ventriculostomy has become the method of choice in the management of occlusive hydrocephalus. The treatment is accompanied by significantly less peri-operative complications than the cerebrospinal fluid shunting procedures previously employed. Close surveillance of patients, however, is necessary to avoid the consequences of raised intracranial pressure that may develop in case of obstruction of the artificial outlet of the 3rd ventricle. The aim of this study was to confirm the value of transcranial Doppler-determined pulsatility index (pI) in the assessment of the patency of endoscopic 3rd ventriculostomy and to elucidate its usefulness in early postoperative recognition of increased intracranial pressure. Methods. In twenty-two patients suffering from occlusive hydrocephalus, transcranial Doppler sonography (TCD) was performed before, immediately after, and five days after endoscopic fenestration of the floor of the 3rd ventricle. PI was defined with fast Fourier transformation. Mean PI values were determined in both middle cerebral arteries (MCA), over five cardiac cycles. Results. In nineteen cases, PI values showed a significant decrease immediately as well as five days after the intervention as compared to the pre-operative values, and flow-sensitive MRI confirmed the patency of the fenestration in all cases. In one patient the operation failed to produce an effective diversion of cerebrospinal fluid as shown by flow-sensitive MRI, and the pulsatility index was unchanged. In two patients, a significant immediate postfenestration drop in PI was followed by a recurrence of PI to pre-operative levels without any clinical deterioration. Conclusions. Preliminary results suggest that the transcranial Doppler-determined pulsatility index is a useful non-invasive tool for the evaluation of the patency of the fenestration in the early follow-up of patients who underwent endoscopic third ventriculostomy.

Allelic polymorphism of GSTM1 and NAT2 genes modifies dietary-induced DNA damage in colorectal mucosa.

Typically, cancer is caused by the interaction of genetic and environmental factors. In colorectal carcinogenesis, diet and nutritional habits are the most important external risk determinants. Allelic polymorphisms of certain metabolizing enzymes may have an influence on cancer risk by modifying the concentration of active carcinogenic compounds in the body. In the present study we investigated the interaction between nutritional and genetic susceptibility factors in human colon carcinogenesis. Healthy volunteers were divided into four groups, based on allelic polymorphisms of N-acetyltransferase 2 and glutathione-S-transferase M1 enzymes. Comet assay was used to determine the level of DNA strand breaks in exfoliated colorectal mucosal cells, following a 2-day vegetarian diet, and after switching to a 2-day ‘high-meat’ diet. The ‘high-meat’ diet statistically significantly increased the amount of single-strand breaks in rapid acetylators and among individuals with a GSMT1+ genotype, while it caused only a slight and not significant increase in the other groups. Our study emphasizes the importance of using susceptibility markers in cancer epidemiology, since environmental effects are strongly modified by these genetic factors.