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Biomedical subjects

A Pollak

Publications and source records attributed to A Pollak.

At least 19 recordsLinked to original sources

Recurrent apical ballooning despite treatment with verapamil.

OBJECTIVE: To report a case of recurrent tako-tsubo syndrome that developed despite treatment with calcium channel antagonists. CASE SUMMARY: A 76-year-old woman with past medical history of ischemic heart disease and mild chronic asthma presented in 2001 with clinical characteristics and laboratory markers consistent with myocardial ischemia. Coronary angiogram was done with successful balloon angioplasty to LAD stenosis. Ventriculogram and echocardiography demonstrated apical ballooning believed to represent aneurysm formation. Several months later, a follow-up echocardiogram (ECG) revealed normal LV size and function with no wall motion abnormalities. ECG was unremarkable. In 2004, the patient was admitted with dyspnea, chest pain and ST elevation in ECG with normal troponin. Coronary angiogram demonstrated patent coronary tree. Left ventriculogram revealed apical ballooning sparing the base of the heart. Medically controlling the asthma attack led to clinical, echocardiographic and remarkable electrocardiographic normalization within days. Rest thallium perfusion scan done within 48 h demonstrated isolated fully reversible defect in the apex after 24 h suggesting a microvessel etiology. CONCLUSION: Tako-tsubo cardiomyopathy is an increasingly recognized condition. We report here the first case of tako-tsubo recurrence despite treatment with verapamil, and suggest a microvessel pathophysiology supported by rest thallium scan.

Aged↗

Cytoskeleton changes following differentiation of N1E-115 neuroblastoma cell line.

No systematic approach to detect expression of differentiation-related elements was published so far. The undifferentiated N1E-115 neuroblastoma cell line was switched into a neuronal phenotype by DMSO treatment and used for proteomic experiments. We used two-dimensional gel electrophoresis followed by unambiguous mass spectrometrical identification of proteins to generate a map of cytoskeleton proteins (CPs), i.e., to search for differentiation-related structures. Alpha-actin, actin-like protein 6A, gamma-tubulin complex component 2, tubulin alpha 3/alpha 7, CLIP associating protein 2, B4 integrin interactor homolog were detectable in the undifferentiated cell line exclusively and neuron-specific CPs drebrin and presynaptic density protein 95, actin-related protein 2/3, alpha and beta-centractin, PDZ-domain actin binding protein, actinin alpha 1, profilin II, ezrin, coactosin-like protein, transgelin 2, myosin light polypeptide 6, tubulin alpha 2, 6 and 7, beta tubulin (94% similar with tubulin beta-2), tubulin beta 3, tubulin tyrosine ligase-like protein 1, lamin B1 and keratin 20 were observed in the differentiated cell line only. We herein identified differentiation-related expressional patterns thus providing new evidence for the role of CPs in the process of neuronal differentiation.

Animals↗

Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1.

BACKGROUND: Probiotic lactic acid bacteria (LAB) are able to modulate the host immune system and clinical trials have demonstrated that specific strains have the capacity to reduce allergic symptoms. Therefore, we aimed to evaluate the potential of recombinant LAB producing the major birch pollen allergen Bet v 1 for mucosal vaccination against birch pollen allergy. METHODS: Recombinant Bet v 1-producing Lactobacillus plantarum and Lactococcus lactis strains were constructed. Their immunogenicity was compared with purified Bet v 1 by subcutaneous immunization of mice. Intranasal application of the live recombinant strains was performed to test their immunomodulatory potency in a mouse model of birch pollen allergy. RESULTS: Bet v 1 produced by the LAB was recognized by monoclonal anti-Bet v 1 and IgE antibodies from birch pollen-allergic patients. Systemic immunization with the recombinant strains induced significantly lower IgG1/IgG2a ratios compared with purified Bet v 1. Intranasal pretreatment led to reduced allergen-specific IgE vs enhanced IgG2a levels and reduced interleukin (IL)-5 production of splenocytes in vitro, indicating a shift towards non-allergic T-helper-1 (Th1) responses. Airway inflammation, i.e. eosinophils and IL-5 in lung lavages, was reduced using either Bet v 1-producing or control strains. Allergen-specific secretory IgA responses were enhanced in lungs and intestines after pretreatment with only the Bet v 1-producing strains. CONCLUSIONS: Mucosal vaccination with live recombinant LAB, leading to a shift towards non-allergic immune responses along with enhanced allergen-specific mucosal IgA levels offers a promising approach to prevent systemic and local allergic immune responses.

Administration, Intranasal↗

Molecular background of polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome in a Polish population: novel AIRE mutations and an estimate of disease prevalence.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal-recessive autoimmune disease caused by autoimmune regulator gene mutations. The aim of this study was to examine the mutation profile of Polish APECED patients, determine the carrier rate of the most frequent mutation(s) and estimate disease prevalence. While studying 14 unrelated patients, we identified three novel mutations (c.1A>T, affecting the start codon; [IVS1 + 1G>C; IVS1 + 5delG], a complex mutation affecting splice site; c. 908G>C, p.R303P, a missense mutation in plant homeodomain (PHD) and three previously reported mutations (c.769C>T, p.R257X; c.967_979del13bp, C322fsX372; c.931delT, p.C311fsX376). Eleven patients had mutations on both chromosomes, whereas in three patients only a single alteration with proven or likely pathogenic effect was detected. The most frequent was the p.R257X mutation (71% of chromosomes); its carriage rate was assessed in the background population. Analysis of 2008 samples showed eight heterozygotes, indicating the frequency of 0.40% (1:250) and the disease prevalence - 1:129,000 (95% confidence interval: 1:555,000 to 1:30,000). Comparison with an epidemiological estimate (1:619,000, derived for women) suggested that in Poland, APECED is underdiagnosed. Among the patients, no genotype/phenotype correlations were found, but we noted that women had earlier onset of hypoparathyroidism (p < 0.02) and were younger at diagnosis (p < 0.05) than men.

Adolescent↗

The neuronal differentiation process involves a series of antioxidant proteins.

Involvement of individual antioxidant proteins (AOXP) and antioxidants in the differentiation process has been already reported. A systematic search strategy for detecting differentially regulated AOXP in neuronal differentiation, however, has not been published so far. The aim of this study was to provide an analytical tool identifying AOXP and to generate a differentiation-related AOXP expressional pattern. The undifferentiated N1E-115 neuroblastoma cell line was switched into a neuronal phenotype by DMSO treatment and used for proteomic experiments: We used two-dimensional gel electrophoresis followed by unambiguous mass spectrometrical (MALDI-TOF-TOF) identification of proteins to generate a map of AOXP. 16 AOXP were unambiguously determined in both cell lines; catalase, thioredoxin domain-containing protein 4 and hypothetical glutaredoxin/glutathione S-transferase C terminus-containing protein were detectable in the undifferentiated cells only. Five AOXP were observed in both, undifferentiated and differentiated cells and thioredoxin, thioredoxin-like protein p19, thioredoxin reductase 1, superoxide dismutases (Mn and Cu-Zn), glutathione synthetase, glutathione S-transferase P1 and Mu1 were detected in differentiated cells exclusively. Herein a differential expressional pattern is presented that reveals so far unpublished antioxidant principles involved in neuronal differentiation by a protein chemical approach, unambiguously identifying AOXP. This finding not only shows concomitant determination of AOXP but also serves as an analytical tool and forms the basis for design of future studies addressing AOXP and differentiation per se.

Animals↗

Mass spectrometrical analysis of human serine racemase in foetal brain.

We analysed human serine racemase for the first time from human foetal brain by mass spectrometrical methods, MALDI MS and MS/MS. The detection of human serine racemase from a transient area of human foetal brain, the perireticular nucleus, that is suggested to be mainly involved in guidance of corticofugal and thalamocortical fibers, may be a clue for the important role of this enzyme in neuronal migration and brain development via regulation of NMDA receptor activity.

Amino Acid Sequence↗

[Integrated psychological parental assistance in the neonatal intensive care unit: concepts and first experiences].

BACKGROUND AND HYPOTHESIS: Psychosocial support programs have been established in view of the burden caused to parents having their newborn admitted to the neonatal intensive care unit (NICU). Due to limited resources, preventive programs can only be offered to parents who are identified by the staff to be at risk. Based on the results of a parent questionnaire, the University Children's Hospital Vienna has developed a standardized concept of integrated psychological support. The program and first results are presented. PATIENTS AND METHODS: The psychological support is offered to parents of newborns admitted to the neonatal intensive care unit. The aim of the support is to avoid later psychosocial problems for child and parents. In an interdisciplinary collaboration, the psychologist facilitates parent-child bonding, family development and coping with the baby's illness. The standardized psychological support consists of a consultation at the beginning and end of the hospital stay. Parents are offered optional psychological support or intensive assistance. RESULTS: Parents from 152 patients received the standardized basic psychological support. The majority of the parents took advantage of the additional optional assistance. Because of external transfers (42.1 %) or infant death (18.4 %), only 39.5 % of the parents could be accompanied until discharge. CONCLUSIONS: A standardized psychological model provides parents with the psychological support as one important part of the overall concept of neonatal treatment. Additionally, the medical and nursing staff were sensitized to psychological factors. An effective psychosocial prevention requires psychological support as an essential part of intensive neonatal care.

Adaptation, Psychological↗

Caesarean section following the Fontan procedure: two different deliveries and different anaesthetic choices in the same patient.

The Fontan procedure is performed for patients with a hypoplastic right ventricle, and pregnancies following this palliative surgery are likely to increase. We present a parturient with the Fontan physiology who successfully underwent two consecutive caesarean deliveries; the first under general anaesthesia for emergency surgery and the second under regional anaesthesia for elective surgery. We suggest that pregnancy and delivery do not typically adversely affect maternal cardiac status in these patients. Attention must be paid, however, to fetal loss, prematurity, growth retardation and associated cardiac congenital malformations for which insufficient data exist in the literature in this patient population.

Adult↗

Association between congenital toxoplasmosis and preterm birth, low birthweight and small for gestational age birth.

OBJECTIVE: To determine the association between congenital toxoplasmosis and preterm birth, low birthweight and small for gestational age birth. DESIGN: Multicentre prospective cohort study. SETTING: Ten European centres offering prenatal screening for toxoplasmosis. POPULATION: Deliveries after 23 weeks of gestation in 386 women with singleton pregnancies who seroconverted to toxoplasma infection before 20 weeks of gestation. Deliveries after 36 weeks in 234 women who seroconverted at 20 weeks or later, and tested positive before 37 weeks. METHODS: Comparison of infected and uninfected births, adjusted for parity and country of birth. MAIN OUTCOME MEASURES: Differences in gestational age at birth, birthweight and birthweight centile. RESULTS: Infected babies were born or delivered earlier than uninfected babies: the mean difference for seroconverters before 20 weeks was -5.4 days (95% CI: -1.4, -9.4), and at 20 weeks or more, -2.6 days (95% CI: -0.5, -4.7). Congenital infection was associated with an increased risk of preterm delivery when seroconversion occurred before 20 weeks (OR 4.71; 95% CI: 2.03, 10.9). No significant differences were detected for birthweight or birthweight centile. CONCLUSION: Babies with congenital toxoplasmosis were born earlier than uninfected babies but the mechanism leading to shorter length of gestation is unknown. Congenital infection could precipitate early delivery or prompt caesarean section or induction of delivery. We found no evidence for a significant association between congenital toxoplasmosis and reduced birthweight or small for gestational age birth.

Abortion, Induced↗

Lack of correlation between fatty acid oxidation disorders and haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome?

AIM: Fatty acid beta-oxidation defects comprise a heterogeneous group of disorders that may precipitate acute life threatening metabolic crises particularly during catabolic episodes. Several studies have demonstrated a possible association between fatty acid beta-oxidation defects, including long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and severe pregnancy complications. However, the precise percentage of women with haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome associated with foetal fatty acid beta-oxidation defects is not known. METHODS: We carried out a multicentre retrospective study on 88 infants, born to women with HELLP syndrome. Acylcarnitine profiles from blood dried on filter paper cards were analysed by tandem mass spectrometry for the diagnosis of fatty acid beta-oxidation defects. In addition, we screened for the common long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency mutation using a standard restriction fragment length polymorphism polymerase chain reaction method. RESULTS: None of the infants studied carried the common long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency mutation. There was no evidence of fatty acid beta-oxidation defects, including long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, as expected by unremarkable acylcarnitine profiles, while three infants with fatty acid beta-oxidation defects were diagnosed in the control group. CONCLUSIONS: Neither foetal long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, including heterozygosity for the common long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency mutation, nor fatty acid beta-oxidation defects in general are a major risk factor for HELLP syndrome in Austria.

3-Hydroxyacyl CoA Dehydrogenases↗

Brain abscesses after Serratia marcescens infection on a neonatal intensive care unit: differences on serial imaging.

Serratia are known to be a possible cause of severe cerebral infections in neonates. We describe imaging of three premature infants infected with Serratia marcescens. Born in the 31( st), 25( th) and 28( th) weeks of gestation, they presented with signs of septicaemia on postnatal days 9, 24 and 32. Initial sonography showed cysts in the first child, two areas with anechoic centre and echogenic rim in the second, and several echogenic areas in the third. Lesions were seen on CT, of low density in two cases and minimally increased density in the third. MRI in the first patient showed cysts with incomplete contrast enhancement of the lesions, while patient 2 showed five ring-enhancing fluid-containing lesions with thick walls. In the third patient two abscesses with contrast enhancement and several high-signal spots were seen. We discuss the pathophysiology of the lesions and the impact of the various imaging methods.

Brain Abscess↗

Evaluation of an amikacin loading dose for nosocomial infections in very low birthweight infants.

AIM: To develop a simplified amikacin dosage regimen for nosocomial infections in preterm infants including a loading dose in order to achieve therapeutic Maximum Serum Concentrations early in the course of therapy. METHODS: Open, non-comparative study during November 2000 to April 2001. The modified amikacin dosing and monitoring protocol included a loading dose of 10 mg/kg in the first week of life, followed by a maintenance regimen of 7.5 mg/kg every 24 h. After the first week of life the corresponding doses were 17 mg/kg (loading) and 15 mg/kg (maintenance). A peak level was measured 30 min after the second dose, a trough level immediately before the third dose. RESULTS: Twenty-five very low birthweight infants (median birthweight 739 g, median gestational age 25 wk) who had 34 episodes of amikacin treatment were included in the analysis. Median amikacin peak and trough values were 37.1 micromol/l and 6.3 micromol/l, respectively. Twenty-nine of all peak levels (85%) and 30 of all trough levels (88%) were within the targeted range of >35 micromol/l and <8.5 micromol/l, respectively. All patients with elevated trough levels were of extremely low birthweight and were born in the 24th week of gestation. Hearing evaluations were performed in 17 of 19 surviving infants at discharge home, all of which gave normal results. CONCLUSION: The new amikacin dosing protocol yielded targeted peak and trough concentrations in a high percentage of very low birthweight infants with nosocomial infection after the first week of life. Our simplified dosage regimen achieved acceptable serum concentrations in all birthweight and gestational age groups, with the exception of extremely low birthweight infants weighing less than 700 g and/or with a gestational age of 24 wk or less. Only limited information can be gained from our data regarding the use of amikacin during the first week of life.

Amikacin↗

Preterm male infants need more initial respiratory support than female infants.

UNLABELLED: Female infants have a significantly greater chance of surviving than male infants at similar birthweights and gestational ages, and have an advantage over males for a better outcome with less morbidity. CONCLUSION: The exact mechanisms responsible for the gender differences, with a better chance of survival of female infants, remain to be determined. The paper by Elsmén et al. provides an important contribution to this most important area of clinical research.

Clinical Trials as Topic↗

A novel technique to measure position-dependent resistance changes in the vertebral arteries postmortem: new insights into the aetiology of SIDS?

AIM: A central respiratory regulation disturbance--triggered by impaired oxygen supply to the brainstem--is being discussed as an aetiological factor in sudden infant death syndrome. In this experimental study, further insight was sought into how far cervical spine movements may induce critical narrowing of the vertebral arteries. METHODS: In 10 infant bodies, the vertebral arteries were cannulated close to their origin and perfused with a fluid bolus of 5 ml in 2 s. The intravascular peak pressure created was memorized. Individual resistance indices were computed for every vertebral artery by relating the average pressure maximum from 10 measurements each with maximal rotation of the neck to either side alone and then with additional hyperextension of the cervical spine to the average peak pressure in neutral head position. RESULTS: Alterations of position-induced pressure changes occurred in the vertebral arteries of all children. Considering exclusively the combined movements of rotation plus extension, resistance increased ipsi- and contralaterally--no matter which side the head was turned--in three infants. A further three reacted with resistance surges only contralateral to the direction of rotation, and one only ipsilateral. Double contralateral associated with only one-directional ipsilateral rise was observed twice, and vice versa once. CONCLUSION: The presented method enables crude quantification of postmortem dynamic resistance alterations in the vertebral arteries. How far such measurements reflect authentic circulatory conditions during life remains to be assessed.

Autopsy↗

Influence of the route of sensitization on local and systemic immune responses in a murine model of type I allergy.

The pathophysiological and immunological characteristics of allergic immune responses are controlled by a variety of factors. We have studied the extent to which the route of sensitization influences allergen-specific IgE synthesis and local airway inflammation using a mouse model of allergic sensitization to the major birch pollen allergen Bet v 1. Sensitization of BALB/c mice with recombinant (r)Bet v 1 was performed using intraperitoneal (i.p.), subcutaneous (s.c.) or aerosol (a.s.) sensitization protocols. Mice were analysed for allergen-specific serum antibodies by ELISA and IgE-dependent basophil degranulation. Proliferative responses and cytokine production of splenocytes were measured upon Bet v 1 stimulation in vitro. Bronchoalveolar lavages were performed after airway challenge with aerosolized birch pollen extract for assessment of eosinophilic airway inflammation and local cytokine production in vivo. Highest allergen specific IgE levels and IgE-dependent basophil degranulation were achieved using the SC route. High IL-5 production by spleen and lung cells was associated with pronounced eosinophilia in bronchoalveolar lavages. After i.p. sensitization, despite giving the highest IgG levels, only low IgE levels, basophil degranulation and IL-5 production were seen. On the other hand, a.s. sensitization, resulting in the lowest systemic IgE and IL-5 levels, led to a comparably strong airway inflammation as the s.c. route. Our finding that the route of sensitization can result in a dissociation of local and systemic immune responses may contribute to a better understanding of the pathogenesis of allergic diseases and help to develop new treatment strategies.

Aerosols↗

Safety evaluation of piperacillin/tazobactam in very low birth weight infants.

An open, non-comparative study was designed to evaluate the safety and tolerance of parenteral piperacillin/tazobactam in very low birth weight infants. Twenty-seven patients were included for nosocomial sepsis with gram-negative bacteria (n = 4), nosocomial sepsis not responding to the empirical antibiotic regimen (n = 3), suspected necrotizing enterocolitis (n = 17), and infection after abdominal surgery for reasons other than necrotizing enterocolitis (n = 3). No clinical adverse events considered related to the study drug were noted, in particular, no cases of phlebitis, rash or stool changes. Several possibly related, mild and transitory abnormalities of laboratory parameters were observed. No long-lasting effect on the intestinal flora was detected. Seventeen patients (63%) were considered to have a favorable clinical response. This study demonstrates that piperacillin/tazobactam is a safe and well tolerated drug for preterm infants with bacterial infections, particularly those involving the gastrointestinal tract. Comparative clinical trials are warranted to further clarify the microbiological efficacy of piperacillin/tazobactam in this particular patient population.

Anti-Bacterial Agents↗

Magnetic resonance imaging in foetuses with bilateral moderate ventriculomegaly and suspected anomaly of the corpus callosum on ultrasound scan.

OBJECTIVE: The diagnosis of anomalies of the corpus callosum (ACC) in foetuses with bilateral moderate ventriculomegaly (BMV) is difficult by means of ultrasound scan. The aim of this study was to examine the value of the additional investigation with magnetic resonance imaging (MRI) in foetuses with BMV and suspected ACC on ultrasound scan. Pathogenesis and clinical presentation of BMV and ACC are discussed. METHODS: 41 foetuses with central nervous system (CNS) anomalies on ultrasound scan were assessed by ultrasonography and MRI from 1999 to 2001. Eight of these 41 foetuses presented with BMV and suspected ACC on ultrasound scan and were prospectively included in the study. Foetal investigations with sonography and MRI were analysed with regard to diagnostic confidence; results were correlated with post partum findings. Six of these 41 foetuses presented with BMV without suspected ACC on ultrasound scan and were retrospectively analysed. RESULTS: Ultrasonography suspected ACC in 8 foetuses with BMV. MRI confirmed the presence of ACC in 4 of these 8 cases. MRI additionally showed ACC in two of the six retrospectively analysed foetuses with BMV without suspected ACC on ultrasound scan. Prenatal MRI diagnosis was confirmed after delivery in all cases. CONCLUSION: MRI is more sensitive than ultrasonography in the evaluation of ACC in foetuses with BMV. For prenatal screening ultrasound still remains the investigation of choice.

Adult↗