Anorectal malformations and pregnancy-related disorders: a registry-based case-control study in 17 European regions.

OBJECTIVE: To identify pregnancy-related risk factors for different manifestations of congenital anorectal malformations (ARMs). DESIGN: A population-based case-control study. SETTING: Seventeen EUROCAT (European Surveillance of Congenital Anomalies) registries, 1980-2008. POPULATION: The study population consisted of 1417 cases with ARM, including 648 cases of isolated ARM, 601 cases of ARM with additional congenital anomalies, and 168 cases of ARM-VACTERL (vertebral, anal, cardiac, tracheo-esophageal, renal, and limb defects), along with 13 371 controls with recognised syndromes or chromosomal abnormalities. METHODS: Multiple logistic regression analyses were used to calculate adjusted odds ratios (ORs) for potential risk factors for ARM, such as fertility treatment, multiple pregnancy, primiparity, maternal illnesses during pregnancy, and pregnancy-related complications. MAIN OUTCOME MEASURES: Adjusted ORs for pregnancy-related risk factors for ARM. RESULTS: The ARM cases were more likely to be firstborn than the controls (OR 1.6, 95% CI 1.4-1.8). Fertility treatment and being one of twins or triplets seemed to increase the risk of ARM in cases with additional congenital anomalies or VACTERL (ORs ranging from 1.6 to 2.5). Maternal fever during pregnancy and pre-eclampsia were only associated with ARM when additional congenital anomalies were present (OR 3.9, 95% CI 1.3-11.6; OR 3.4, 95% CI 1.6-7.1, respectively), whereas maternal epilepsy during pregnancy resulted in a five-fold elevated risk of all manifestations of ARM (OR 5.1, 95% CI 1.7-15.6). CONCLUSIONS: This large European study identified maternal epilepsy, fertility treatment, multiple pregnancy, primiparity, pre-eclampsia, and maternal fever during pregnancy as potential risk factors primarily for complex manifestations of ARM with additional congenital anomalies and VACTERL.

H1 tau haplotype-related genomic variation at 17q21.3 as an Asian heritage of the European Gypsy population.

In this study, we examine the frequency of a 900 kb inversion at 17q21.3 in the Gypsy and Caucasian populations of Hungary, which may reflect the Asian origin of Gypsy populations. Of the two haplotypes (H1 and H2), H2 is thought to be exclusively of Caucasian origin, and its occurrence in other racial groups is likely to reflect admixture. In our sample, the H1 haplotype was significantly more frequent in the Gypsy population (89.8 vs 75.5%, P<0.001) and was in Hardy-Weinberg disequilibrium (P=0.017). The 17q21.3 region includes the gene of microtubule-associated protein tau, and this result might imply higher sensitivity to H1 haplotype-related multifactorial tauopathies among Gypsies.

MtDNA polymorphism in the Hungarians: comparison to three other Finno-Ugric-speaking populations.

Mitochondrial DNA sequence variation as well as restriction site polymorphisms were examined in 437 individuals from four Finno-Ugric-speaking populations. These included the Hungarians (Budapest region and the Csángós from Hungary and Romania), the Finns and two Saami groups from northeastern Finland (Inari Saami and Skolt Saami), and the Erzas from central Russia. The mtDNA data obtained in this study were combined with our previous data on Y chromosomal variation for eight different loci in these populations. The genetic variation observed among the Hungarians resembled closely that found in other European populations. The Hungarians could not be distinguished from the neighboring populations (e.g., the Austrians) any more than from their Finno-Ugric linguistic relatives.

MtDNA and Y chromosome polymorphisms in Hungary: inferences from the palaeolithic, neolithic and Uralic influences on the modern Hungarian gene pool.

Magyars imposed their language on Hungarians but seem not to have affected their genetic structure. To better investigate this point, we analysed some mtDNA and Y chromosome polymorphisms in a sample of the Hungarian Palóc who, for historical reasons, could have retained genetic traces of Magyars more than other groups. In addition, we examined a mixed sample from Budapest. About 100 individuals were tested for the markers defining all the European and Asian mtDNA haplogroups and about 50 individuals for some Y chromosome markers, namely the 12f2 and 49a,f/TaqI RFLPs, the YAP insertion, the microsatellites YCAIIa, YCAIIb, DYS19 and the Asian 50f2/C deletion. In the mtDNA analysis only two subjects belonged to the Asian B and M haplogroups. The Y chromosome analyses showed that the Palóc differed from the Budapest sample by the absence of YAP+ allele and by the DYS19 allele distribution; that the proto-European 49a,f Ht 15 and the neolithic 12f2-8Kb were rather uncommon in both groups; that there is a high prevalence of the 49a,f Ht 11 and the YCAII a5-b1; and that the Asian 50f2/C deletion is absent. These results suggest that the influence of Magyars on the Hungarian gene pool has been very low through both females and males and the Hungarian language could be an example of cultural dominance. Alternative explanations are discussed. An expansion centred on YAP-, 49a,f Ht 11 is revealed by the median network based on compound haplotypes. 49a,f Ht 11 could represent either a paleolithic marker of eastern Europe which underwent expansion after the last glacial period, or a marker of the more recent spread of the Yamnaia culture from southern Ukraine.

Probable ancestors of Hungarian ethnic groups: an admixture analysis.

The history of Hungary starts in the 9th century with the arrival of the Magyars in the Carpathian Basin. They spoke, like modern Hungarians, an Uralic language belonging to the Finno-Ugric language group. Their original composition probably included Iranian and Turkish people, while other populations were already present in the territory (Avars, Slavs, Germans). Some of the Hungarian ethnic groups claim to be descendants of ancient Magyars settlers (such as the Orség), others of Huns, Turks or Iranians. We collected and compared the previously published gene frequencies of eight ethnic groups and seven hypothetical ancestral populations, including Uralics, applying a model of admixture. The results, most of which confirm historical hypotheses or the oral tradition, show that only one ethnic group (Orség) highly resembles the Uralic population.

Y chromosomal polymorphisms reveal founding lineages in the Finns and the Saami.

Y chromosomal polymorphisms were studied in 502 males from 16 Eurasian ethnic groups including the Finns, Saami (Inari Lake area and Skolt Saami), Karelians, Mari, Mokshas, Erzas, Hungarians (Budapest area and Csángós), Khanty, Mansi, Yakuts, Koryaks, Nivkhs, Mongolians, and Latvians. The samples were analysed for polymorphisms in the Y chromosome specific Alu insertion (YAP) and six microsatellites (DYS19, DYS389-I and II, DYS390, DYS392, DYS393). The populations were also screened for the recently described Tat polymorphism. The incidence of YAP+ type was highest in the Csángós and in other Hungarians (37.5% and 17.5%, respectively). In the Karelians and the Latvians it was present at approximately the same level as commonly found in other European populations, whilst absent in our further samples of Eurasian populations, including the Finns and the Saami. Aside from the Hungarians, the C allele of the Tat polymorphism was common in all the Finno-Ugric speaking populations (from 8.2% to 63.2%), with highest incidence in the Ob-Ugrian Khanty. The C allele was also found in the Latvians (29.4%). The haplotypes found associated with the Tat C allele showed consistently lower density than those associated with the T allele, indicating that the T allele is the original form. The computation of the age of the Tat C suggested that the mutation might be a relatively recent event giving a maximum likelihood estimate of 4440 years (95% confidence interval about 3140-6200 years). The distribution patterns of the 222 haplotypes found varied considerably among the populations. In the Finns a majority of the haplotypes could be assigned to two distinct groups, one of which harboured the C allele of the Tat polymorphism, indicating dichotomous primary source of genetic variation among Finnish males. The presence of a bottleneck or founding effect in the male lineages of some of the populations, namely in the Finns and the Saami, would appear to be one likely interpretation for these findings.

Genetic structure in relation to the history of Hungarian ethnic groups.

The present analysis continues the study of 12 samples of 11 Hungarian ethnic groups and a collection of data from 8 foreign reference populations. The origin of these groups is entangled with the history of Hungary and specifically with the conquest of the Carpathian basin in the ninth century A.D. Given that each of the 11 groups has preserved its ethnic identity and assuming that genetic drift has played a major role, we expect that similarities and differences between the different Hungarian groups and between the Hungarian groups and the eight reference populations can be interpreted with respect to the controversial origin of the groups. The reference populations are those whose ancestors had high involvement in Hungarian history. We use multivariate statistical methods to analyze the gene frequencies of 22 loci. The results show that the Hungarian ethnic groups are genetically separate and that this separation is related to different migration waves. According to our results, Gypsies and Jews, who migrated relatively recently to Hungary, are distant from the other groups and, as predicted, appear to be genetically close to the North Indian and Ashkenazi reference populations, respectively. The Oriental population is least related to the Hungarian groups, but the distance diminishes when the P1 locus, which shows particularly high variability, is included. Some ethnic groups, especially Orség and Csángó, show genetic isolation and specific affinities with the reference populations that are related to their origin, namely, Slavs and Finns-Turks-Iranians, respectively. Other affinities were less striking than tradition would lead us to expect. Gene flow and admixture, as revealed by the significant correlation between genetic and geographic distances, may have played an important role in smoothing genetic differences between groups.

A trace element preparation containing zinc increases the production of interleukin-6 in human monocytes and glial cells.

The in vitro effects of a trace element preparation (béres Drops Plus, BDP) on the biosynthesis of inflammatory cytokines interleukin (IL-6, IL-1, and tumor necrosis factor-alpha (TNF-alpha) were studied in human peripheral monocytes. The production of IL-6 was studied in a glioblastoma cell line, SKMG-4, as well. The trace element preparation BDP significantly stimulated both the constitutive and the endotoxin or IL-1 induced IL-6 production in monocytes or in glial cells, respectively, but revealed no or only modest effect on IL-1 and TNF-alpha production of monocytes. Moreover, BDP was able to reduce the inhibitory effect of a synthetic corticosteroid, dexamethasone on the biosynthesis of IL-6. The positive effect of the trace element preparation on the IL-6 production of monocytes from rheumatoid arthritis (RA) patients is comparable, to that of on the monocytes from healthy individuals, and similarly to healthy individuals was negligible on the IL-1 and TNF-alpha production. The detailed analysis of the composition of the preparation suggested, that the major active component in the stimulation of IL-6 production is Zn, but for the complete effect other trace elements are also required.

Serum protein and erythrocyte enzyme polymorphisms in twelve population groups of Hungary.

The distribution of the serum proteins C3, TF, HP, GC, BF, AMY2, PLG, GM, and KM and the erythrocyte enzyme polymorphisms GLO, GPT, ESD, ACP, 6-PGD, ADA, AK, PGM1 and PGP amongst twelve population groups in Hungary was investigated. Gene frequencies and genetic distances are discussed in relation to the present geographical locations of these groups and their probable history of migration.

Alcohol use, abuse, and alcohol-related disorders among ethnic groups in Hungary. Part I: Csángós from Egyházaskozár Region.

This paper reports the results of a study on alcohol drinking habits, alcohol-related acute symptoms, and alcohol abuse among Csángós, an ethnic minority in Hungary. The demographic data revealed their social characteristics: growing old, low education, endogamous marriages, early maternal age at birth of the first baby, and a high child number per family. Alcohol use survey revealed that alcohol consumption of the Csángós is considerably high; more than half of Csángó males and more than one-quarter of Csángó females are heavy drinkers. While all kinds of alcohol are consumed by males, wine drinking is more common among females. Acute reactions to a moderate dose of alcohol evoked a series of physical and physiological symptoms including facial flushing, higher pulse rate, tachycardia and euphoria among at least one third of the probands. There was a distinct gender difference in response to alcohol drinking. While a higher percentage of females reported intense skin flush (34%), a greater percentage of males reported symptoms such as sleepiness, euphoria and aggressiveness. The distribution of clinical chemical markers of alcohol abuse in the sera of the individuals under study confirmed heavier alcohol consumption among males than among females. Alcohol-related mortality data indicate liver cirrhosis and liver cancer as the leading cause of deaths among Csángó males. A high alcohol consumption among Csángó ethnic group reflects the acceptance of alcohol use in the community as an integral part of their lifestyle.

Alcohol use, abuse, and alcohol-related disorders among ethnic groups in Hungary. Part II: Palócs from Mátraderecske.

An epidemiological study on alcohol drinking habits, alcohol metabolism rate, alcohol-related acute physiological symptoms, and alcohol misuse among Palócs, an ethnic minority in Hungary, was conducted. The demographic and sociocultural correlates revealed their ethnic identity: low to moderate education, relatively low number of children per family and higher percentage of skilled workers among males. Alcohol use survey revealed that frequency of alcohol consumption among Palóc male population is considerably high. While about 41% of the Palóc males reported to drink daily between 30 ml and 90 ml pure alcohol, only 5% of the females reported to consume this amount regularly. 53% of males and less than 1% of females were classified as heavy drinkers (consuming more than 60 ml absolute alcohol per day). While all kinds of alcoholic beverage was reported to be consumed by the males, Pálinka (a kind of brandy) drinking was more common among females. About 45% of the Palócs reported to experience acute reactions after drinking a moderate dose of alcohol. The physical and physiological reactions include facial flushing, higher pulse rate, tachycardia and euphoria. While there was no distinct gender difference in facial flushing response to alcohol drinking, a higher percentage of males (70%) reported symptoms such as sleepiness, euphoria and aggressiveness as compared to about only 36% females reporting such reactions. Distribution of clinical chemical markers, in particular GGT values confirmed a heavier alcohol consumption among males than among females. High GGT value also correlated with a positive alcohol-related facial flushing reaction in males.

The number of glucocorticoid receptors in peripheral human lymphocytes is elevated by a zinc containing trace element preparation.

A trace element preparation (Béres Drops Plus, BDP) elevates the number of glucocorticoid receptors (gcR) in peripheral lymphocytes isolated both from healthy blood donors and rheumatoid arthritis patients. This enhancement by BDP was found either for constitutive expression of gcRs or in experiments when the lymphocytes were stimulated by interleukin (IL)-6. There was no significant effect of BDP on IL-1 and tumour necrosis factor alpha (TNF alpha)-induced changes of gcRs. The effect of BDP was greatly dependent on the presence of Zn++ ions in the preparation, since the augmenting effect was abolished if BDP did not contain zinc.

Preeclampsia related to a functioning extrauterine placenta: report of a case and 25-year follow-up.

We report the case of a patient with preeclampsia due to an extrauterine, intra-abdominal pregnancy. After the fetus was delivered, but while the functioning placenta remained in the abdomen, preeclampsia, which was documented by clinical data and a kidney biopsy, persisted until the placenta was removed 99 days postpartum. A kidney biopsy 21 months postpartum was normal. Twenty-five years later, her kidney function and blood pressure were normal. The observation of this patient supports the view that the placenta must be intact for the development of preeclampsia and is the first description of endotheliosis in a kidney biopsy from a hypertensive woman with an intra-abdominal pregnancy.

[Genetic traits in the area of Bodrogköz]. / Genetikai jellegek vizsgálata a Bodrogközben.

In 1984 a late malaria endemic area, called Bodrogköz was studied. This was a reexamination of the population genetic work performed by Walter, Nemeskéri. In six villages of Bodrogköz 328 persons were tested for AB0, Rh blood groups, haptoglobins, haemoglobin concentration, haematocrit, erythrocyte amount, the MCV, the MCH and the G-6-PD were analyzed. The quantitative determination of HbF and HbA2, red cell osmotic resistance and thalassemia were measured as well. Thalassemia heterozygote carriers and an increased level of HbF were revealed. The frequency of G-6-PD deficiency was 0.39%. In Bodrogköz the frequencies of AB0, Rh and haptoglobin types were similar in the present and all previous studies. The background of this similarity might be the genetic similarity between two following generations. On the basis of these facts, the Hb0 Arab and partially DNA work we suggested an alternative hypothesis that these mutant genes got into Bodrogköz by the rather later migration than with ancient Hungarian people during the period of conquest of Hungary.

Clinical outcome of continuous ambulatory peritoneal dialysis predicted by urea and creatinine kinetics.

The effectiveness of urea kinetics (Kt/V, where K is urea clearance, t is treatment time, and V is the volume of distribution for urea) to assess the adequacy of continuous ambulatory peritoneal dialysis (CAPD) and clinical outcome has not been established prospectively, and cross-sectional clinical studies have been inconclusive. A minimum weekly creatinine clearance of 40 to 50 L is recommended, but the adequacy of this dose is unproven. We introduced a simpler approach to creatinine kinetics in the form of an efficacy number (EN) calculated from data obtained in a standardized 4-h dwell exchange. To determine the most effective model for predicting CAPD adequacy, residual renal function, weekly Kt/V urea, weekly creatinine clearance standardized to body surface area, and EN (liters per gram of creatinine per day) were measured in 18 stable CAPD patients followed prospectively for at least 12 months. Patients were divided into three groups, good (G), intermediate (I), and poor (P), on the basis of uremic symptoms, mortality, hospital days, biochemical indices, and the need for transfer to hemodialysis. When comparing groups G (N = 6) and P (N = 8), weekly Kt/V were 2.3 +/- 0.2 versus 1.5 +/- 0.1 (P less than 0.005), weekly creatinine clearances were 71.5 +/- 8.6 versus 35.1 +/- 1.3 L (P less than 0.001), and EN were 7.4 +/- 0.8 versus 3.6 +/- 0.2 L/g of creatinine/day (P less than 0.005). Creatinine kinetics (weekly clearance and EN) but not urea kinetics could differentiate group I (N = 4) from groups G or P. Both urea and creatinine kinetics predict clinical outcome in CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

De novo complex chromosomal rearrangement in a woman with recurrent spontaneous abortion and one healthy daughter.

Although rare, complex chromosomal rearrangements have been reported in the literature. The result is multiple congenital malformations in the offspring and recurrent spontaneous abortion. Chromosome 7 is usually involved, but in our patient chromosome 18 was involved.

Concomitant incidence of fertility chance reducing varicocele and chromosome aberration.

Authors describe the case of a male patient with varicocele, oligozoospermatism and subfertility, a 46 XY t (8; 10) (q22; p15) balanced chromosome carrier. Following varicectomy, successful pregnancy has developed even with balanced translocation meaning only 50% fertility chance. Prenatal diagnostics by chorion biopsy showed a fetus of normal chromosome constellation. Authors call attention to the fact that even minor, step-by-step improvements in fertility chance may lead to success in multiple aberrations.

Stereospecific synthesis and antiviral properties of different enantiomerically pure carbocyclic 2'-deoxyribonucleoside analogues derived from common chiral pools: (+)-(1R,5S)- and (-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one.

Enantiomerically pure (+)- and (-)-carbocyclic thymidine, (-)-carbocyclic 3'-epi-thymidine, (+)-carbocyclic 3'-deoxy-3'-azidothymidine, (+)-carbocyclic 2,3'-O-anhydrothymidine, (+)-carbocyclic 3'-O,6'-methylenethymidine, and (+)-(6'S)-carbocyclic 6'-methylthymidine were synthesized in a stereospecific manner from common chiral pools of (+)-(1R,5S)- and (-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one and evaluated for antiviral activity. (+)-Carbathymidine and, to a lesser extent, (+)-carbocyclic 2'-deoxyadenosine proved to be effective against HSV-1 [minimum inhibitory concentration (MIC): 0.2 and 2 micrograms/mL, respectively] and HSV-2 (MIC: 2 and 20 micrograms/mL, respectively), but virtually inactive against TK- HSV-1 (MIC: 40 and 100 micrograms/mL, respectively). (+)-Carbathymidine was also active against vaccinia virus (2 micrograms/mL). None of the compounds had a specific effect on the replication of HIV or other RNA viruses.

A method to assess efficacy of CAPD: preliminary results.

Adequacy of dialysis is a primary concern when caring for patients undergoing continuous peritoneal dialysis (CAPD). To determine objectively the efficacy of CAPD, the use of an 'efficacy number' (EN) calculated from the data obtained in a peritoneal equilibration test (PET) for creatinine (cr) is proposed: EN = [cr(D/P) x V24] divided by ACPPD3 Where, cr(D/P) is PET-derived dialysate/plasma ratio for creatinine at 4 hrs; V24 is the volume of exchanges (L) prescribed for 24 hrs; ACPPD is adjusted creatinine production based on daily dialysate creatinine appearance. PET were performed and the EN calculated in two groups of CAPD patients observed over a 10 month period. One group (n = 8) had a poor clinical outcome in terms of uremic parameters. The EN in this group was 3.85 +/- 0.45 (+/- 1 SD) L/g creatinine/day. The other group (n = 4) was considered well dialyzed and had a good clinical outcome over 10 months. The EN in this group was 6.07 +/- 0.40 L/g creatine/day, p less than 0.001. There was no statistically significant difference between the two groups in regard to sex, age, length of time on dialysis, underlying kidney disease, baseline creatinine, or D/P ratios of creatinine and BUN. The 'efficacy numbers' appears to be more useful than the D/P ratio alone in determining the adequacy of CAPD. A simple to use nomogram is presented which provides guidelines for the clinician to alter the dialysis prescription.