Outcome of esophageal atresia in Germany.

The aim of this study was to evaluate the outcome of esophageal atresia in Germany in a retrospective observational study of a large cohort. Data from the major health insurance company in Germany, which covers approximately 30% of German patients, were analyzed. All patients born and registered between 2009 and 2013 with a diagnosis of esophageal atresia at first admission to the hospital were included. Mortality was analyzed during the first year of life. We identified 287 patients with esophageal atresia, including 253 with and 34 without tracheoesophageal fistula. Associated anomalies were found in 53.7% of the patients; the most frequent were cardiac anomalies (41.8%), anomalies of the urinary tract (17.4%), and atresia of the colon, rectum, and anus (9.4%). Forty-one patients (14.3%) had a birth weight <1500 g. Seventeen patients (5.9%) died before surgery. Gastrostomy was performed during the index admission in 70 patients (25.9%). The reconstruction of the esophageal passage was performed in 247 patients (93.9%). Forty-eight percent of the patients who underwent an operation required dilatation. The mortality rate in the patients who underwent an operation was 10.4%. These results from Germany correspond to the international results that have been reported. The number of dilatations was in the middle of the range of those reported in the literature; the overall mortality rate was in the upper portion of the range of the international rates. Efforts should be made to establish a clinical registry to measure and improve the quality of care for this and other rare conditions.

Loss of promoter IV-driven BDNF expression impacts oscillatory activity during sleep, sensory information processing and fear regulation.

Posttraumatic stress disorder is characterized by hyperarousal, sensory processing impairments, sleep disturbances and altered fear regulation; phenotypes associated with changes in brain oscillatory activity. Molecules associated with activity-dependent plasticity, including brain-derived neurotrophic factor (BDNF), may regulate neural oscillations by controlling synaptic activity. BDNF synthesis includes production of multiple Bdnf transcripts, which contain distinct 5' noncoding exons. We assessed arousal, sensory processing, fear regulation and sleep in animals where BDNF expression from activity-dependent promoter IV is disrupted (Bdnf-e4 mice). Bdnf-e4 mice display sensory hyper-reactivity and impaired electrophysiological correlates of sensory information processing as measured by event-related potentials (ERP). Utilizing electroencephalogram, we identified a decrease in slow-wave activity during non-rapid eye movement sleep, suggesting impaired sleep homeostasis. Fear extinction is controlled by hippocampal-prefrontal cortical BDNF signaling, and neurophysiological communication patterns between the hippocampus (HPC) and medial prefrontal cortex (mPFC) correlate with behavioral performance during extinction. Impaired fear extinction in Bdnf-e4 mice is accompanied by increased HPC activation and decreased HPC-mPFC theta phase synchrony during early extinction, as well as increased mPFC activation during extinction recall. These results suggest that activity-dependent BDNF signaling is critical for regulating oscillatory activity, which may contribute to altered behavior.

Percentiles of Lymphocyte Subsets in Preterm Infants According to Gestational Age Compared to Children and Adolescents.

Preterm newborns show an increased susceptibility to infections, conceivably related to their immature immune system. To gain further knowledge about the immune development in early preterm infants, we aimed to establish references for lymphocyte subsets and compare the maturation process during hospitalization to healthy term-born children and adolescents. For this purpose, peripheral blood samples (n = 153) were collected from 40 preterm infants, gestational age (GA) 26-30 week between 2nd and 6th day of life, and were monitored in intervals of every 2 or rather 4 weeks until the end of hospitalization. Furthermore, we analysed single sample controls of 10 term neonates. We compared these data with results of a study in healthy children and adolescent (n = 176). Flow cytometry of immune cell subsets was performed as single-platform analysis using 10-colour flow cytometry. Based on preterm's age, our percentile model allows readout of absolute cell count for lymphocytes, B cells, T cells, NK cells, T8 and T4 cells. The median (minimum) value of T-, B- and NK cells after birth was 2800 (600), 790 (120) and 140 (20) cells/µl, respectively. Major differences were found in absolute cell numbers of B cells, and in the frequency of regulatory T cells, most pronounced in the earliest preterm infants (GA 26). Compared to healthy children and adolescents, preterm infants reached lymphocyte counts in between the 5th and 50th percentile when discharging the hospital. This prospective observational study provides reference percentiles for lymphocytes subsets of preterm infants. These data are conducive to interpret immunological capability of preterm infants with possible immune disorders appropriate.

Ziprasidone--not haloperidol--induces more de-novo neurogenesis of adult neural stem cells derived from murine hippocampus.

INTRODUCTION: Here, we present a stem-cell based study on the de-novo generation of beta-III-tubulin-positive neurons after treatment with the classic antipsychotic drug haloperidol or after treatment with the second-generation antipsychotic (SGA) ziprasidone. METHODS: Adult neural stem cells (ANSC) dissociated from the adult mouse hippocampus were expanded in cell culture with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). ANSC differentiated upon withdrawal of EGF and bFGF. RESULTS AND DISCUSSION: Ziprasidone generated significantly more beta-III-tubulin-positive neurons than haloperidol during the differentiation of adult neural stem cells isolated from murine hippocampus (ANSC). We assume that this net increase in neurogenesis by ziprasidone relies on this drug's 5-HT1A receptor affinity, which is not present in the haloperidol molecule, since the inactivation by WAY100621 impeded this process. These data could possibly suggest a clinical relevance for studying antipsychotic drugs in the stem cell paradigm employed in this study.

Three-dimensional body scanning: a new method to estimate body surface area in neonates.

BACKGROUND: Body surface area (BSA) is usually estimated by calculation with mathematical formulae. Three-dimensional body scanning (3D scan) offers a suitable alternative. OBJECTIVES: We determined the BSA in healthy term and near-term neonates by 3D scanning. This system should be useful in the setting of intensive care medicine. METHODS: The measuring system consisted of a projector, two cameras, mirrors and a computer, and used the fringe projection technique with visible light. The infants were examined in a supine position; the hidden parts of the bodies were corrected for using a mathematical factor developed with a baby doll model. Results of the 3D scans were compared with those from five mathematical formulae for each subject. RESULTS: A total of 209 infants were studied by 3D scanning, of whom 53 had acceptable images and were selected for further analysis. The mean BSA was 2,139 cm(2) (SD 223.72). The minimal BSA was 1,587 cm(2), the maximal 2,670 cm(2), with a good correlation to body weight and length. One mathematical formula (Du Bois and Du Bois) showed a distinct underestimation of BSA compared to 3D scanning, the others an overestimation. Mean percentage similarity was from 96.8 to 100.9%. CONCLUSIONS: 3D scanning is an accurate and practical method to estimate BSA in newborns. Individual and repeated measurements from day to day are possible. Further studies are warranted in preterm and sick neonates.

Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress.

The subgranular zone of the adult hippocampal dentate gyrus contains a pool of neural stem cells that continuously divide and differentiate into functional granule cells. It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression. The survival of newly born hippocampal neurons is decreased by chronic psychosocial stress and increased by exposure to enriched environments. These observations suggest the existence of a link between hippocampal neurogenesis, stress-induced behavioral changes, and the beneficial effects of enriched environment. To show causality, we subjected transgenic mice with conditionally suppressed neurogenesis to psychosocial stress followed by environmental enrichment. First, we showed that repeated social defeat coupled with chronic exposure to an aggressor produces robust and quantifiable indices of submissive and depressive-like behaviors; second, subsequent exposure to an enriched environment led to extinction of the submissive phenotype, while animals exposed to an impoverished environment retained the submissive phenotype; and third, enrichment was not effective in reversing the submissive and depressive-like behaviors in transgenic mice lacking neurogenesis. Our data show two main findings. First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis.

Evidence for the involvement of the kainate receptor subunit GluR6 (GRIK2) in mediating behavioral displays related to behavioral symptoms of mania.

The glutamate receptor 6 (GluR6 or GRIK2, one of the kainate receptors) gene resides in a genetic linkage region (6q21) associated with bipolar disorder (BPD), but its function in affective regulation is unknown. Compared with wild-type (WT) and GluR5 knockout (KO) mice, GluR6 KO mice were more active in multiple tests and super responsive to amphetamine. In a battery of specific tests, GluR6 KO mice also exhibited less anxious or more risk-taking type behavior and less despair-type manifestations, and they also had more aggressive displays. Chronic treatment with lithium, a classic antimanic mood stabilizer, reduced hyperactivity, aggressive displays and some risk-taking type behavior in GluR6 KO mice. Hippocampal and prefrontal cortical membrane levels of GluR5 and KA-2 receptors were decreased in GluR6 KO mice, and chronic lithium treatment did not affect these decreases. The membrane levels of other glutamatergic receptors were not significantly altered by GluR6 ablation or chronic lithium treatment. Together, these biochemical and behavioral results suggest a unique role for GluR6 in controlling abnormalities related to the behavioral symptoms of mania, such as hyperactivity or psychomotor agitation, aggressiveness, driven or increased goal-directed pursuits, risk taking and supersensitivity to psychostimulants. Whether GluR6 perturbation is involved in the mood elevation or thought disturbance of mania and the cyclicity of BPD are unknown. The molecular mechanism underlying the behavioral effects of lithium in GluR6 KO mice remains to be elucidated.

[Management of HIV-positive pregnancies -- results from a retrospective study]. / Geburtshilfliches Management bei HIV-positiven Schwangeren: Ergebnisse einer retrospektiven Analyse an einem integrativen Zentrum.

OBJECTIVE: The management of HIV-positive pregnancies was investigated in conjunction to pre-, peri and postpartal complications and the HIV transmission rate. PATIENTS AND METHODS: Retrospective study of 88 HIV-positive patients who were delivered at the Dept. of Obstetrics and Gynaecology during 1.1.1997-31.12.2001. RESULTS: HIV-positive patients showed significantly more prepartal complications, compared to control group. Low CD4-cell count (< or = 200/microl) or high viral load (> 10 000 HIV-copies/ml) was not associated with increased risk for transmission relevant complications. The overall HIV-transmission rate was 3.4 % (3/89 newborns; with ART 2.5 % [2/85], without ART 33.3 % [1/3]). The transmission rate increased with complications during pregnancy (7.7 % [2/26] vs. 1.6 % [1/61]). Newborns delivered < or = 35 (th) week of gestation showed a transmission rate of 5.3 % compared to 2.9 % of newborns delivered after the 35 (th) week of gestation. 98 % of the patients were delivered by cesarean section (primary: n = 71, prior: n = 15), spontaneously: n = 2). 97 % of patients (85/88) were treated with antiretroviral therapy (ART). No differences were found in the postpartal complication rate of HIV-positive to -negative patients. None of the newborns was breast fed. CONCLUSIONS: Treatment of this risk-pregnancies in HIV experienced centers significantly reduces the risk of HIV transmission.

Safety and immunogenicity of an acellular pertussis vaccine in premature infants.

OBJECTIVES: To evaluate the safety and immunogenicity of a two-component acellular pertussis vaccine in preterm infants. STUDY DESIGN: Fifty preterm infants (25-35 weeks of gestation; mean, 30.8 weeks) and 50 term infants as a control group received a two-component acellular pertussis vaccine irrespective of their biological age and actual weight. Adverse reactions were registered by parents on a diary card and reviewed on each visit. Antibodies against pertussis toxoid (PT) and filamentous hemagglutinin (FHA) were determined with an enzyme-linked immunosorbent assay before the first and after the third vaccination. RESULTS: The infants of both groups showed an increase in geometric mean titers (GMT) against PT and FHA after vaccination (3 doses). There was a significant difference of antibody concentration between the preterm and the control group. The GMT for PT antibody of the preterm infants was 64. 16 U/L, and for the term infants it was 98.96 U/L. The GMT for FHA was 50.92 U/L in preterm versus 86.02 U/L in the control group. Efficacy of the immunization (more than a fourfold increase of antibody concentration in each infant) was 93.5% in the preterm group with respect to PT and 82.6% with respect to FHA. The incidence of adverse reactions was low and comparable in both study groups. CONCLUSION: Immunization with an acellular pertussis vaccine is safe for preterm infants. The immune response is significantly lower compared with a control group of term infants, but efficacy is high.

Invasive pulmonary aspergillosis in a critically ill neonate: case report and review of invasive aspergillosis during the first 3 months of life.

We report a fatal case of invasive pulmonary aspergillosis in a severely ill neonate and review 43 additional cases of invasive aspergillosis reported from 1955 through 1996 that occurred during the first 3 months of life. Eleven of the 44 patients had primary cutaneous aspergillosis, 10 had invasive pulmonary aspergillosis, and 14 had disseminated disease. Most infections were nosocomial in origin. Prematurity (43%); proven chronic granulomatous disease (14%); and a complex of diarrhea, dehydration, malnutrition, and invasive bacterial infections (23%) accounted for the majority of underlying conditions. At least 41% of the patients had received corticosteroid therapy before diagnosis, but only one patient had been neutropenic. Among patients who received medical and/or surgical treatment, outcome was relatively favorable, with an overall survival rate of 73%. Invasive aspergillosis may occur in neonates and young infants and warrants consideration under certain circumstances. Current therapeutic approaches consist of high-dose amphotericin B and appropriate surgical interventions.

Glutamate modulation of dopamine measured in vivo with positron emission tomography (PET) and 11C-raclopride in normal human subjects.

Subanesthetic doses of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine exacerbate psychosis in schizophrenic patients, and ketamine has significant abuse liability. These observations indicate that a secondary effect of ketamine may be to increase dopamine concentrations. The present study was undertaken using positron emission tomography (PET) and the dopamine (D2) radiotracer 11C-raclopride to determine whether ketamine would decrease D2 receptor availability, indicative of an increase in dopamine concentrations. Two scans were performed in seven male control subjects before and after administration of ketamine (0.5 mg/kg, i.v. infused over 20 min). Ketamine significantly increased cortisol levels and decreased dopamine receptor availability in the striatum (specific binding), but not in the cerebellum (nonspecific binding). In addition, the cerebellar binding subtracted from the striatal binding (to account for changes in nonspecific binding) was significantly decreased after ketamine administration. These results provide in vivo evidence for the ability of ketamine to increase striatal dopamine concentrations, consistent with the role of the NMDA receptor in modulating dopamine function.

Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects.

OBJECTIVE: This study was undertaken to measure serotonergic modulation of dopamine in vivo by using positron emission tomography (PET), a radiotracer for the striatal dopamine D2 receptor ([11C]raclopride), and a pharmacologic challenge of the serotonin system (d,l-fenfluramine). METHOD: Two PET studies using [11C]raclopride were performed in 11 normal male subjects before administration of the serotonin-releasing agent and reuptake inhibitor fenfluramine (60 mg p.o.) and 3 hours afterward. A graphical analysis method was used with the [11C]raclopride data to derive the distribution volume of D2 receptors. Plasma levels of fenfluramine, norfenfluramine, homovanillic acid (HVA), cortisol, and prolactin were determined. RESULTS: Levels of fenfluramine and prolactin were elevated 2 hours after fenfluramine administration and remained significantly elevated during the second scan, while levels of HVA and cortisol were not altered significantly during the time of scanning. A significant decrease in the specific binding (striatum) and the nonspecific binding subtracted from the specific binding (striatum minus cerebellum) of [11C]raclopride was observed. The rate of metabolism of [11C]raclopride and the nonspecific binding (cerebellum) were not significantly altered by the fenfluramine intervention. CONCLUSIONS: The observed decrease in [11C]raclopride binding is consistent with an increase in dopamine concentrations and with the ability of serotonin to stimulate dopamine activity. The ability to measure serotonergic modulation of dopamine in vivo may have implications for the study of etiologic and therapeutic mechanisms in schizophrenia, major depressive disorder, obsessive-compulsive disorder, and substance abuse.

The study of neurotransmitter interactions using positron emission tomography and functional coupling.

Functional brain imaging with positron emission tomography (PET) has opened up new avenues for the investigation of possible functional disturbances related to psychiatric disease as well as pharmacodynamic assessment of drug treatment in vivo. Different strategies to study pharmacologic effects on the brain have been developed in recent years. The basic methods are to measure (a) blood flow or glucose metabolism, (b) parameters of specific receptor binding, or (c) neurotransmitter metabolism. Each of these can be performed either in a resting state or after perturbation with a pharmacologic challenge. Our group has developed a general strategy for investigating pharmacologic effects on brain function: (a) determining indirect drug-induced metabolic changes with fluorodeoxyglucose PET and (b) characterizing functional interactions of neurotransmitter systems by assaying drug-induced displacement of specific receptor ligands. These study designs reflect a paradigm shift where functional coupling of brain regions and interaction of different neurotransmitter systems are seen as the basis for a multitransmitter hypothesis of schizophrenia. In this view, any disturbance in the self-regulatory process is reflected in the loss of functional interaction between systems. An overview of recent studies and their possible clinical importance will be presented.

Decreased benzodiazepine receptor binding in panic disorder measured by IOMAZENIL-SPECT. A preliminary report.

Single photon emission tomography (SPECT) imaging of the central benzodiazepine receptor (BZr) became possible with the newly developed ligand 123I-IOMAZENIL. The BZr binding was investigated in ten patients with panic disorder (PP) compared to ten epileptic patients (EP). Panic patients had lower IOMAZENIL uptake rates in the frontal, occipital and temporal cortex than EP indicating the involvement of the BZr complex in panic disorder.

[Persistent pulmonary hypertension in the newborn infant caused by aneurysm of the vein of Galen]. / Persistierende pulmonale Hypertension des Neugeborenen bei Aneurysma der Vena Galeni.

A male full-term neonate is described in whom cardiac insufficiency developed within 24 hours post partum. Ultrasound revealed an arterio-venous fistula of the vein of Galen. The patient's condition did not allow surgical correction and he died on the 22nd day of life. Persistent pulmonary hypertension was an important accompanying feature. The literature is reviewed with respect to the prognosis and the up to now seldom reported complication of persistent pulmonary hypertension of the newborn (PPHN).

An outbreak of Acinetobacter calcoaceticus infection in a neonatal care unit.

Between January and December 1988, 383 neonates were admitted to our neonatal intensive care unit. 1,991 swabs and blood cultures were tested bacteriologically. Among them 90 specimens obtained from 41 patients were positive for Acinetobacter calcoaceticus. During this period we discovered and treated three cases with A. calcoaceticus sepsis. Three additional cases had blood cultures positive for this bacterium without demonstrating any clinical signs of infection. There is good evidence that contaminated warm air humidifiers were the source of infection. A review of microbiological data for several months preceding the outbreak showed a definite increase in the presence of A. calcoaceticus. The affected neonates required specific antibiotic therapy and intensive care. All of them survived. Conditions favoring the spread of these generally non-pathogenic bacteria and modes of preventive measures are discussed. The necessity of continuous bacteriological surveillance and careful disinfection of intensive care equipment is emphasized.