Differences in attentional functioning between preterm and full-term children underline the importance of new neuropsychological detection techniques.

AIM: The aim of this study was to investigate specific attentional components in preterm born children who had not yet started school. METHODS: Between January and December 2011, we assessed 52 preterm and 52 full-term children aged between five years five months and six years two months, of comparable age and gender, at the Medical University of Vienna. Different attentional components were evaluated through selected subtests of the Test of Attentional Performance and the German version of the Wechsler Intelligence Scale for Children. Each child's behaviour was also evaluated using parental ratings and descriptive item-based evaluation during neuropsychological assessment. RESULTS: Children born preterm showed poor attentional performance in sustained attention, focused attention and distractibility, as well as reductions in processing speed in divided attention and flexibility tasks. Children born preterm also showed decreased volitional attention compared with automatic attention. No problems were detected in alertness or inhibition. In addition, a higher rate of aborted tests, decreased motivation and poorer parental ratings were detected among the preterm population compared with full-term born children. CONCLUSION: Our results highlighted differences in attentional functioning between preterm and full-term children, indicating the importance of new neuropsychological techniques for the detection of specific attentional disorders.

Amniocentesis for the detection of congenital toxoplasmosis: results from the nationwide Austrian prenatal screening program.

Prenatal diagnosis of congenital toxoplasmosis (CT) influences therapeutical management in pregnant women and their offspring. In Austria, a nationwide serological healthcare program to identify potential maternal toxoplasma infections during pregnancy exists. We assessed the clinical use of amniocentesis for toxoplasma-specific polymerase chain reaction (PCR) on amniotic fluid to detect CT. Data on serology, amniocentesis, PCR, complications, treatment, and paediatric clinical outcome were collected retrospectively among the birth cohort 1992-2008. There were 1386 women with amniocentesis, but only in 707 cases (51%) was acute maternal infection confirmed serologically. A high proportion (49%) of amniocenteses with negative PCR results in women with chronic infection or seronegativity were performed without clinical justification for the women or their foetuses. The positive and negative predictive values of PCR were 94.4% and 99.3%, respectively. Thirty-nine foetuses with CT, including four deaths, were reported. The five PCR-negative but infected infants were identified by the serological and clinical follow-up program. Thirty percent of amniocenteses were performed in the third trimester, and gestational age or treatment did not influence PCR sensitivity. Amniocentesis is indicated in women with acute maternal infection, and facilitated targeted therapies in pregnant women and their offspring. In women with late toxoplasma infection, negative amniotic fluid PCR made treatment of infants unnecessary. Serological and clinical follow-up of infants is important to confirm the infection status of the infant. Recommendations, based on our 17-year experience, to improve the current diagnostic strategies and to reduce unnecessary amniocentesis, are given.

Association of fetal and maternal carboxyhemoglobin levels in normal and Rh-alloimmune pregnancies.

OBJECTIVE: To compare paired antepartum fetal/maternal COHb ratios in whole blood from control and alloimmunized pregnancies and to examine the relationships between fetal and maternal COHb. METHODS: COHb levels were measured in paired fetal and maternal blood samples obtained at cordocentesis in 47 control and 16 Rh-alloimmunized pregnancies. COHb was determined by gas chromatography. Results were analyzed by t-test, regression and analysis of covariance. RESULTS: Although fetal/maternal COHb ratios for control and alloimmunized pregnancies were not statistically significantly different, i.e. 1. 11+/-0.04 and 1.26+/-0.09, respectively (P=0.09), fetal COHb levels were higher in Rh-alloimmunized fetuses (P=0.0002). Fetal COHb levels were also higher than paired maternal levels among the alloimmunized group (P=0.011), but not among the control group (1. 04+/-0.04, P=ns). In univariate regression analysis, fetal and maternal COHb levels were significantly correlated with one another in both control (r=0.52, P=0.0002) and alloimmunized pregnancy groups (r=0.52, P=0.05). Comparison of the slopes of the fetal versus maternal COHb plots for the two groups showed a significant difference (P=0.02), with the alloimmunized group having the steeper slope. CONCLUSION: Differences in the antepartum fetal-maternal COHb relationships in control and alloimmunized groups likely reflect increased endogenous CO production among alloimmunized fetuses as a result of pathologic hemolysis.

A method to derive the time of onset of infection from serological findings.

Among the diagnostic problems requiring a retrospective assessment of the time an event occurred is that of screening for primary infection with Toxoplasma gondii acquired during pregnancy. We suggest a method to derive the possible times of onset of infection from a small sequence of serological samples by matching them against the knowledge about possible courses of infection. Special care is taken to properly address the relative change of consecutive samples, a nontrivial problem when reasoning about sparsely sampled time courses. To investigate the practicability of our approach we conducted a retrospective and a simulated prospective evaluation based on the samples of 394 pregnancies, randomly selected from our toxoplasmosis database; we could demonstrate an overall accuracy of 95.7%.

Microparticle enzyme immunoassay (MEIA) for toxoplasma specific immunoglobulin G in comparison to the Sabin-Feldman dye test. A pilot study.

The microparticle enzyme immunoassay (MEIA) for detection of Toxoplasma specific IgG antibodies was compared to the Sabin-Feldman dye test (DT) as reference in 843 serum samples from a cohort of 757 pregnant women. The overall correlation for individual measurements was highly significant (R = 0.9446, p < 0.0001). DT and specific IgM combined allowed definition of 3 groups of patients: group 1 (no infection), group 2 (latent infection), group 3 (acute infection). A significant difference was found between the groups for the corresponding IgG values, as determined by the MEIA method, which allowed the following cut-off points to be laid down: group 1: 0-5.2 IU/ml, group 2: 5.3-187.5, and group 3: 187.6 IU/ml and higher. The validity of the cut-off points was tested in a subgroup of 57 patients who underwent serological follow-up during pregnancy. All 15 acutely- and 14 non-infected women, as well as 25 out of 28 latent infections were identified correctly. 3 latent infection were allocated falsely as acute. The threshold values presented in this report need to be confirmed in a large prospective study.

[Toxoplasmosis diagnosis in pregnancy: computer assisted follow-up interpretation of serologic tests]. / Toxoplasmose-Diagnostik in der Schwangerschaft: Computerunterstützte Verlaufsinterpretation von serologischen Tests.

Primary infection with Toxoplasma gondii during pregnancy can result in fetal infection with serious sequelae for the unborn if not treated properly. Early diagnosis enables drug therapy and significantly reduces the risk of fetal disease. A systematic serological screening procedure was established in Austria in 1975 to detect primary toxoplasma infection as early as possible during pregnancy. Since the screening program is based solely on observation and interpretation of serological data, the question arises whether a knowledge-based system for automatic interpretation can achieve a sufficient interpretative accuracy for introduction to routine work. For this reason the system Toxopert-I was developed. The system is aimed at facilitating routine laboratory work, as well as assuring quality by setting standards for therapy. The required knowledge base was designed as a knowledge graph, each state representing a certain interpretation. One or more available serological test results cause the knowledge graph to change its current state. If all available test results are processed, the final state reached corresponds to the respective current interpretation for the patient. A retrospective analysis of 1000 pregnant women yielded a total diagnostic sensitivity and specificity of over 99% in comparison with the clinician's diagnosis which was used as the Gold Standard.

[Direct detection of Toxoplasma gondii with polymerase chain reaction in diagnosis of fetal toxoplasma infection]. / Direkter Nachweis von Toxoplasma gondii mit Polymerase-Kettenreaktion zur Diagnostik einer fetalen Toxoplasma-Infektion.

Primary infection with Toxoplasma gondii during pregnancy may affect the fetus and result in congenital toxoplasmosis. In Austria serological screening for detection of newly acquired infection during pregnancy was introduced in 1975. In this study we used polymerase chain reaction (PCR) for detection of fetal infection with Toxoplasma gondii. Amniotic fluid samples were analyzed from 11 women with serological indication of acute toxoplasmosis infection. Nine of these women had already received treatment prior to amnio-centesis and no evidence of Toxoplasma gondii DNA was detected with PCR in the respective amniotic fluid samples. Isolation of the organism by mouse inoculation was negative in these cases and follow-up serology as well as clinical examination of the infants confirmed these results. In 2 patients investigation of the amniotic fluid samples by means of PCR was positive; both women had not yet been treated at the time of amniocentesis. Our results indicate that identification of Toxoplasma gondii in amniotic fluid is a useful procedure for diagnosing or excluding fetal infection. Moreover, the current recommendations of the screening program appear to be successful in preventing congenital toxoplasmosis.

Toxopert-I: knowledge-based automatic interpretation of serological tests for toxoplasmosis.

Primary infection with Toxoplasma gondii, a parasite found in most regions of the world, is asymptomatic in more than 80% of cases. However, primary infection with Toxoplasma gondii in a pregnant woman might cause fetal infection and severe damage. Most cases do not require treatment. This applies to women without any infection (denoted as seronegative) and women who have acquired the infection before conception (denoted as latent). In contrast, women with postconceptual infection require immediate treatment to prevent or ameliorate fetal infection. We have developed an expert system, called Toxoport-I, designed for routine laboratory work, which automatically interprets serological test results of toxoplasma infection. By using the system the clinician can also examine questionable cases by interactively exploring possible results. We used a popular method of designing expert systems applied to medical interpretation and therapy advice, the rule-based one. In order to meet the requirements of automatic interpretation in toxoplasma serology the following characteristics were introduced: the interpretation of sequences of test results, the possibility of excluding inconsistent test results and the adaptability of the knowledge base. A decision graph that covers the different kinds of infections as well as therapy and recommendations for further tests was designed, implemented and was clinically tested by carrying out a retrospective study including 1000 pregnant women. A comparison of Toxoport-I and the clinician's interpretations yielded sensitivity and specificity rates of over 99% each.

[Congenital toxoplasmosis retinochoroiditis after primary infection of the mother in pregnancy]. / Konnatale Toxoplasmose retinochoroiditis nach Primärinfektion der Mutter in der Schwangerschaft.

An infection with Toxoplasma gondii during pregnancy means that the unborn baby may be infected as well. In addition to the risk that the baby may be born dead, central chorioretinitis could also occur. Pregnant women with primary infection were treated with spiramycin or a combination of pyrimethamine and sulfadiacine. A total of 153 children (1 month-1 year) were examined twice with particular attention to the macula region. Only two cases showed central retinochoroiditis. In one case the treatment was insufficient, and in the other the time between the serological examinations was too long. None of the other children showed any central pathological changes within the follow-up period. Screening methods, the appropriate treatment and the results are presented.

Knowledge-based interpretation of toxoplasmosis serology test results including fuzzy temporal concepts--the ToxoNet system.

Transplacental transmission of Toxoplasma gondii from an infected, pregnant woman to the unborn that occurs with a probability of about 60 percent [1] results in fetal damage to a degree depending on the gestational age. The computer system ToxoNet processes the results of serological antibody tests having been performed during pregnancy by means of a knowledge base containing medical knowledge on the interpretation of Toxoplasmosis serology tests. By applying this knowledge ToxoNet generates interpretive reports consisting of a diagnostic interpretation and recommendations for therapy and further testing. For that purpose it matches the results of all serological investigations of maternal blood with the content of the knowledge base returning complete textual interpretations for all given findings. The interpretation algorithm derives the stage of maternal infection from these that is used to infer the degree of fetal threat. To consider varying immune responses of particular patients, certain time intervals have to be kept between two subsequent tests in order to guarantee a correct interpretation of the test results. These time intervals are modelled as fuzzy sets, since they allow the formal description of the temporal uncertainties. ToxoNet comprises the knowledge base, an interpretation system, and a program for the creation and modification of the knowledge base. It is available from the World Wide Web by starting a standard browser like the Internet Explorer or the Netscape Navigator. Thus ToxoNet supports the physician in Toxoplasmosis diagnostics and in addition allows to adopt the way of making decisions to the characteristics of the particular laboratory by modifying the underlying knowledge base.

Prenatal magnetic resonance imaging as a useful adjunctive to ultrasound-enhanced diagnosis in case of a giant foetal tumour of the neck.

Large cervical masses in the prenatal period are rare and can cause life threatening situations after birth. All available diagnostic techniques should therefore be used to determine the best mode of delivery in the case of such malformation. A large cervical mass was detected by ultrasound in a 41-year-old women, gravida 4, para 3, at 29 + 5 weeks of gestation. US imaging was most consistent with the diagnosis of a large cervical teratoma, but it was not possible to sufficiently evaluate the cervical anatomy of the oropharynx and trachea. An MRI scan demonstrated a distorted oropharynx and a trachea displaced to the right and posteriorly, but not detectable from the middle of the neck up to the larynx. Based on these facts, an EXIT procedure was planned and performed at 30 + 5 weeks of gestation. Foetal MRI provided valuable anatomical information for all specialists deciding on the indication and the pre-therapeutic planning of the EXIT procedure.

Effects of cornstarch treatment in very young children with type I glycogen storage disease.

Three children aged 1-2 years with glycogenosis type I were treated with 2 g/kg bodyweight oral cornstarch per meal (4-5 times a day) for a period up to 16 months. In comparison to the previous dietary regimen (day and nocturnal feedings every 3 h) the cornstarch diet stabilised serum glucose profiles and dramatically improved secondary hyperlipoproteinaemia. Mean total triglycerides decreased up to one half, consistent with a fall of very low density lipoprotein-triglycerides up to two thirds. Metabolic acidosis and hyperuricaemia did not occur and normal growth rates (0.7-1 cm/month) were achieved. We conclude that the cornstarch regimen even in the age group up to 2 years can be considered as an efficient alternative in the treatment of glycogenosis type I patients with less frequent feedings and without nocturnal infusion.

[Carbohydrates in the treatment of glycogenoses]. / Kohlenhydrate in der Therapie von Glykogenosen.

Glycogen storage diseases (GSD) include inborn errors in glycogen synthesis and degradation which, like most metabolic diseases, evades any therapeutical concept up to now. Nevertheless, in a subgroup of glycogenoses, characterized by functional absence of the key glycogenolytic enzyme glucose-6-phosphatase (GSD-1), dietary treatment is able to ensure almost normal development of affected patients. The principle of treatment consists of oral application of raw cornstarch, which is hydrolyzed slowly in the intestinum resulting in normoglycemia over a period of several hours. Thus, nighttime nasogastric tube-feeding, the standard dietary regimen in GSD-1, could be avoided. Based on our experiences, this therapeutic approach, which has proven successful up to now only in elder children and adults, can be recommended even in children under 2 years of age, if the individual response to an oral starchload has been examined prior to the starch diet.

Plasma concentrations of free amino acids during 3 weeks treatment of massively obese children with a very low calorie diet.

Eight grossly obese children (2 girls, 8 boys, age 12.6 +/- 2.1 mean +/- SD years, mean overweight 73.3 +/- 14%) were treated for 3 weeks with a very low calorie diet (VLCD), containing 1022 kJ/240 kcal, 33 g protein, 25.5 g carbohydrate and 0.7 g fat/day. Mean weight loss after 3 weeks was 9.47 +/- 2.8 kg and mean nitrogen loss was calculated to be 113.3 +/- 71.2 g. While serum electrolytes, enzymes, glucose, urea and creatinine remained almost unchanged, distinct alterations of 23 free amino acids in plasma could be observed. A transient increase of plasma valine, leucine, isoleucine and alpha-aminobutyrate during the 1st week was followed by a constant fall in the 2nd and 3rd week. Glycine, proline, serine and threonine showed a progressive increase, while cystine, histidine and, above all, alanine decreased, the diminution of alanine being most rapid during the 1st week. No significant changes were observed in plasma concentrations of arginine, asparagine, aspartic acid, citrulline, glutamic acid, glutamine, lysine, tyrosine, ornithine, phenylalanine and taurine. Total plasma amino acid content did not change during diet compared to the pre-diet period. The behavior of plasma amino acids shows a typical pattern within four groups, reflecting various interorgan substrate fluxes during hypocaloric dieting.

Non-enzymatic glycation of fetal tissue in diabetic pregnancy. Estimation of the glucitollysine content of umbilical cord extracts.

Non-enzymatic glycation of fetal tissue was studied by determining the glucitollysine content of umbilical cord extracts from twelve infants of diabetic mothers and fourteen infants of healthy, non-diabetic women (controls). The single, glycated amino-acid glycitollysine, which reflects the extent of glycation processes in biological samples, was measured by a standard amino acid ion exchange chromatography followed by reverse phase high pressure liquid chromatography. Infants of diabetic mothers had significantly higher cord glucitollysine levels than infants of control mothers (14.3 + 4.6 vs. 5.5 + 2.1 ng/mg dry tissue; M + SD, p less than 0.001). Moreover, five infants of diabetic mothers with congenital anomalies had strikingly high glucitollysine levels, higher than the mean +4 SD of the controls. We conclude, that non-enzymatic glycation of fetal tissue does occur as a result of an in utero exposure to cumulative glycemia. Major congenital anomalies in diabetic pregnancies are associated with a greater extent of non-enzymatic glycation of umbilical cord tissue.

Low-dose dietary L-arginine increases plasma interleukin 1 alpha but not interleukin 1 beta in patients with diabetes mellitus.

Oral high-dose arginine supplementation is used for the experimental immunotherapy of tissue trauma and sepsis. Yet the adequate dosage required for immunomodulation has to be established and the toxicity of high-dose arginine has not been fully elucidated. Following a protocol for the treatment of diabetic long-term complications (oral daily doses of 30 mg/kg BW; blind, placebo-controlled prospective study with crossing-over design) we studied plasma levels of interleukins 1 alpha (IL-1 alpha) and 1 beta reflecting immunostimulation. Arginine supplementation in 29 patients with diabetes mellitus prompted a 2-fold increase of IL-1 alpha from baseline levels (P < 0.001) while IL-1 beta was unaffected. Implications for the treated panel of diabetic patients could be a reduction of collagen accumulation by enhanced collagenolysis and clearance of advanced-stage non-enzymatic glycosylation products. Based upon our data, low-dose arginine protocols for further immunotherapeutical studies should be discussed.

Follow-up of infants with congenital toxoplasmosis detected by polymerase chain reaction analysis of amniotic fluid.

This study was conducted to assess the validity of performing the polymerase chain reaction (PCR) on amniotic fluid for detecting fetal Toxoplasma infection. The primary endpoint was the outcome of the infant at 1 year of age. A prospective, consecutive study was performed in 49 infants born to mothers with primary Toxoplasma infection during pregnancy. PCR determinations of Toxoplasma gondii DNA in amniotic fluid were carried out as part of their prenatal management. Infants were examined at birth, and at 1, 3, 6, 9, and 12 months of age. Nine of 11 infants from pregnancies with positive PCR results proved to be infected based on follow-up serological investigations conducted during the first year of life. Two fetal deaths occurred. All 38 infants with negative PCR results remained uninfected at 1 year of age, irrespective of whether their mothers had received treatment with sulfadiazine/pyrimethamine or spiramycin alone. Psychomotor development was normal in all infants. This follow-up study confirms that PCR performed on amniotic fluid is a useful method for identification or exclusion of fetal Toxoplasma infection. Treatment of infected pregnant women and - in the event of a positive PCR result subsequent treatment of their infants is associated with a favorable outcome.

[DiGeorge syndrome--significance of early diagnosis in cellular immunodeficiency]. / DiGeorge-Syndrom--Die Bedeutung der Frühdiagnose be zellulären Immundefizienzen.

Di George syndrome is caused by anomalous development of the organs arising from the third and fourth pharyngeal pouches and results in congenital aplasia of the thymus, aplasia or hypoplasia of the parathyroid glands and cardiovascular malformations. Clinically, affected children show hypoparathyroidism and, because of depressed cell-mediated immunity, serious bacterial, viral and fungal infections. We present an infant, aged 6 weeks, with convulsions due to hypocalcemia, in which cell-mediated immunodeficiency was detected. Additionally diagnostic and therapeutic possibilities in DiGeorge syndrome are shown.