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A Schulze

Publications and source records attributed to A Schulze.

At least 37 records · Page 2Linked to original sources
PubMed2004

Air versus oxygen for resuscitation of infants at birth.

BACKGROUND: 100% oxygen is the commonly recommended gas for the resuscitation of infants at birth. There is growing evidence from both animal and human studies that room air is as effective as 100% oxygen and that 100% oxygen may have adverse effects on breathing physiology and cerebral circulation. There is also the theoretical risk of tissue damage due to free oxygen radicals when 100% oxygen is given. The use of room air has, therefore, been suggested as a safer and possibly more effective alternative. OBJECTIVES: In newborn infants requiring resuscitation, does the use of room air reduce the incidence of death, neurological disability and short term morbidity when compared with the use of 100% oxygen? SEARCH STRATEGY: This included searches of the Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004) and MEDLINE PubMed 1966 to December 2003, and handsearches of reference lists of relevant articles and conference proceedings. SELECTION CRITERIA: All randomised and quasi-randomised studies comparing the use of room air or any other concentration of oxygen versus 100% oxygen in the resuscitation of infants at birth. DATA COLLECTION AND ANALYSIS: Three authors assessed the methodological quality of eligible trials and extracted data independently. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. For categorical data the relative risk (RR), risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals (CI) were calculated. Continuous data were analysed using weighted mean difference (WMD). MAIN RESULTS: Five studies were identified which enrolled a total of 1302 infants. In two studies allocation was randomised and the caregivers were blinded to intervention group. In the other three studies, allocation was quasi-randomised and the caregivers were not blinded. Pooled analysis of the four trials reporting effect on death showed a significant reduction in the rate of death in the group resuscitated with room air [typical RR 0.71 (0.54, 0.94), typical RD -0.05 (-0.08, -0.01), NNT 20 (12, 100)]. There were no significant differences between the groups with respect to rates of grade 2 or 3 hypoxic ischaemic encephalopathy. One of the four trials reported a statistically significant difference in median 5 minute Apgar scores, favouring the group allocated to room air. However, the absolute difference between the medians was small and there were no significant differences in the median 10 minute Apgar scores in the three trials reporting this outcome. One trial followed up a selected subgroup of survivors to 18-24 months. There were no significant differences in rates of adverse neurodevelopmental outcomes including cerebral palsy and failure to achieve various milestones; however, the proportion of eligible patients seen was less than 70%. Analyses that were planned for this review, but not able to be carried out because of lack of published data, included a sub-analysis stratified by gestational age and assessments of the effect on bronchopulmonary dysplasia and retinopathy of prematurity. REVIEWERS' CONCLUSIONS: There is insufficient evidence at present on which to recommend a policy of using room air over 100% oxygen, or vice versa, for newborn resuscitation. A reduction in mortality has been seen in infants resuscitated with room air, and no evidence of harm has been demonstrated. However, the small number of identified studies and their methodologic limitations dictate caution in interpreting and applying these results. We note the use of back-up 100% oxygen in more than a quarter of infants randomised to room air. Therefore, on the basis of currently available evidence, if one chooses room air as the initial gas for resuscitation, supplementary oxygen should continue to be made available.

Air↗
PubMed2004

Binding of tritiated and radioiodinated ZM241,385 to brain A2A adenosine receptors.

Autoradiography on rat brain using tritiated (1*), mono- (2*) and di-radioiodinated (3*) derivatives of the A(2A) adenosine receptor antagonist ZM241,385 showed high receptor density in striatum. K(D)s of 1*, 2* and 3* were 0.4, 2.2 and 15 nM and nonspecific binding was 5, 40 and 50% of total binding. Striatal uptake of 2* in mice was approximately 0.2% ID/g 60 min post-injection; blocking by 2 was insignificant. Poor penetration of the blood brain barrier and high nonspecific binding make 2* unsuitable for imaging striatal receptors.

Animals↗
PubMed2004

Effects of inhaled formoterol compared with salbutamol in ventilated preterm infants.

BACKGROUND: Short-acting beta(2)-agonists have shown beneficial effects in preterm infants, but data on long acting beta(2)-agonists are still lacking. OBJECTIVES: To compare the effects of inhaled formoterol with salbutamol in preterm infants. METHODS: Randomized, double-blind, crossover design of salbutamol (100 microg every 6 h) or formoterol (12 microg every 12 h) delivered by metered dose inhaler on two consecutive days to very low birth weight infants on assisted mechanical ventilation (n=12; gestational age 25.7+/-2 weeks; birth weight 720+/-254 g; postnatal age 25+/-9 days; mean+/-SD). Treatment with the second drug was administered until day 7 in eight infants. Outcome variables were minute volume MV, respiratory mechanics, heart rate HR, blood pressure, serum potassium and blood glucose levels. RESULTS: Mean MV increased by maximal 26% (salbutamol) and by 22% (formoterol) differing from baseline values until 6 and 8 h through increased mean tidal volume (Vt) in both groups (max. 14%). Mean static compliance (Crs) increased by 26% (salbutamol) and by 32% (formoterol) until 60 min post-administration. There was no tachyphylaxis. CONCLUSION: Inhaled salbutamol and formoterol equally increase MV, Vt, Crs and HR in mechanically ventilated infants with a longer lasting systemic effect of formoterol.

Administration, Inhalation↗
PubMed2004

Guanidinoacetate methyltransferase deficiency: differences of creatine uptake in human brain and muscle.

Deficiency of guanidinoacetate methyltransferase (GAMT), the first described creatine biosynthesis defect, leads to depletion of creatine and phosphocreatine, and accumulation of guanidinoacetate in brain. This results in epilepsy, mental retardation, and extrapyramidal movement disorders. Investigation of skeletal muscle by proton and phosphorus magnetic resonance spectroscopy before therapy demonstrated the presence of considerable amounts of creatine and phosphocreatine, and accumulation of phosphorylated guanidinoacetate in a 7-year-old boy diagnosed with GAMT deficiency, suggesting separate mechanisms for creatine uptake and synthesis in brain and skeletal muscle. The combination of creatine supplementation and a guanidinoacetate-lowering therapeutic approach resulted in improvement of clinical symptoms and metabolite concentrations in brain, muscle, and body fluids.

Arginine↗
PubMed2004

Neonatal screening for glutaryl-CoA dehydrogenase deficiency.

Acute encephalopathic crisis in glutaryl-CoA dehydrogenase deficiency results in an unfavourable disease course and poor outcome, dominated by dystonia, feeding problems, seizures and secondary complications, and quite often leading to early death. The prerequisite for the prevention of irreversible brain damage in this disease is the detection of affected patients and initiation of treatment before the manifestation of such crisis. Apart from macrocephaly there are no signs or symptoms characteristic for this disease in presymptomatic children and, thus, they are usually missed. In some countries, implementation of extended neonatal screening programmes using electrospray ionization tandem mass spectrometry (ESI-MS/MS) allows detection of affected newborns and start of therapy before onset of neurological complications. This article summarizes recent strategies, pitfalls and shortcomings of a mass screening for glutaryl-CoA dehydrogenase deficiency using ESI-MS/MS. Furthermore, an alternative strategy, namely DNA-based neonatal screening for the Oji-Cree variant of this disease, is demonstrated. An optimization of diagnostic as well as therapeutic procedures must be achieved before GCDH deficiency unequivocally fulfills the criteria of a reliable and successful newborn screening programme.

Amino Acid Metabolism, Inborn Errors↗
PubMed2003

Tetrahydrobiopterin sensitivity in German patients with mild phenylalanine hydroxylase deficiency.

We report the results of tetrahydrobiopterin (BH4) loading tests in 10 German patients with mild phenylketonuria. A significant decline of phenylalanine values after application of BH4 was observed in all but one patients. Molecular genetic analyses revealed a range of different PAH gene mutations. Re-testing of one patient previously reported as non-responsive to BH4 loading showed a moderate response with a higher dose of BH4. Nevertheless, there appear to be kinetic differences in phenylalanine hydroxylation in patients with the same genotype. Non-responsiveness to 20 mg/kg BH4 was observed only in a single patient who was compound heterozygous for the novel mutation R176P (c.527G>C) and the common null-mutation P281L. In summary, our data are in line with recent reports indicating that BH4 sensitivity is a normal feature of most mild forms of PAH deficiency but may be influenced by other factors.

Administration, Oral↗
PubMed2003

[Preserved spontaneous breathing during partial liquid ventilation. Results of experimental animal studies and their clinical implications].

Controlled mechanical ventilation (CMV) may contribute to impaired hemodynamics in patients with respiratory failure. It is rational to assume that hybrid modalities of mechanical ventilation have fewer hemodynamic side-effects when spontaneous respiratory activity is allowed during the application of positive airway pressure. Partial liquid ventilation (PLV) has been shown to improve gas exchange in subjects with severe alveolar lung disease. We have shown that spontaneous respiratory efforts during proportional assist ventilation (PAV) is possible in experimental animals without lung disease whose lungs are partially filled with perfluorocarbons. In another series of experiments we demonstrated that PLV improves oxygenation and lung compliance in adult rabbits with severe surfactant deficiency, and in rabbits with meconium aspiration. In animals with meconium aspiration mortality, work of breathing and the degree of lung injury, as assessed by histological analysis, were reduced. In another two series of animals with and without surfactant deficiency spontaneous breathing supported by PAV was associated with increased cardiac output, stroke volume and oxygen transport, as compared to CMV after pharmacologically induced muscle paralysis. An increased arterial and venous pH in animals with surfactant deficiency during spontaneous breathing supported by PAV suggests improved tissue perfusion. Furthermore, gas exchange was improved during spontaneous breathing supported by PAV as compared to CMV and muscle paralysis.

Algorithms↗
PubMed2003

Validation of an ESI-MS/MS screening method for acylcarnitine profiling in urine specimens of neonates, children, adolescents and adults.

BACKGROUND: Acylcarnitine (AC) profiling in dried blood spots by means of electrospray ionisation tandem mass spectrometry (ESI-MS/MS) has proven to be a useful method in neonatal screening, able to detect inborn errors of fatty acid oxidation, amino acid, organic acid and carnitine metabolism. Furthermore, this method is becoming increasingly applied in selective screening and in prenatal and postmortal diagnostics of inborn metabolic disorders, where urine is commonly used as specimen of interest. We therefore developed and validated a butylation method of acylcarnitine profiling in urine by ESI-MS/MS without previous chromatographic separation. METHODS: Random urine specimens were used for investigation of the analytical imprecision of the method. Recovery, precision and linearity were determined using methanolic standard solutions of free carnitine, octanoylcarnitine and palmitoylcarnitine at various concentrations. RESULTS: The mean coefficients of variation of within-run and run-to-run analysis of these analytes were found between 10% and 20% and demonstrated that the method fulfills the analytical requirements within the relevant ranges of concentration. Creatinine-related and age-related reference values of free carnitine and the ACs (C2-C18) were established. The definite discrimination was possible between patients with fatty acid oxidation disorders, organic acidurias, and healthy controls. The AC profiles from patients with various specific disorders were diagnostically helpful during acute deterioration and even during conditions of well-compensated metabolic state. CONCLUSION: The method used in this study is suitable both for selective screening and for confirmation of diagnosis with the advantage of high-throughput quantitative measurement.

Adolescent↗
PubMed2003

Effects of theophylline on the pattern of spontaneous breathing in preterm infants less than 1000 g of birth weight.

Proportional assist ventilation (PAV) amplifies the ventilatory effect of the spontaneous respiratory effort and therefore allows analysis of drug-induced changes in the spontaneous breathing pattern of subjects who depend on mechanical ventilatory assistance. We hypothesized that theophylline will reduce the number and duration of respiratory pauses and apneic events in infants less than 1000 g of birth weight on PAV. Twelve infants were studied: median birth weight was 773 g; gestational age 26.0 weeks and postnatal age 9 days. Measurements were obtained over a 2-h period before and after 5 mg/kg of intravenous theophylline. A respiratory pause was defined as cessation of breathing for at least the duration of three preceeding breaths. The total number of respiratory pauses and the number of apneas followed by either cardiac slowing (decrease in heart rate more than 10%) or bradycardia decreased significantly. Minute ventilation increased due to a rise in tidal volume from 5.6+/-1.3 to 6.1+/-1.2 ml/kg (p=0.004). The duration of respiratory pauses, the respiratory rate, and the number of apneas followed by desaturation did not change significantly. We conclude that theophylline stimulates spontaneous breathing in infants less than 1000 g, reduces the number of apneas, and increases minute volume by increasing the tidal volumes.

Apnea↗
PubMed2003

Evaluation of radioiodinated 8-Cyclopentyl-3-[(E)-3-iodoprop-2-en-1-yl]-1-propylxanthine ([*I]CPIPX) as a new potential A1 adenosine receptor antagonist for SPECT.

8-Cyclopentyl-3-[(E)-3-[(131)I]iodoprop-2-en-1-yl]-1-propylxanthine (2*) was generated by iododestannylation of the tributyl-stannyl-precursor with [(131)I]NaI and chloramine T. The radiochemical yield of 2* was 82 +/- 4%, and the purity exceeded 98%. The specific activity was 33 +/- 19 GBq/micromol. Affinities for rat, pig and human A(1) adenosine receptors (A(1)ARs) were in the low nanomolar range, but poor selectivity for the human A(1)AR over the A(2A)AR was found. Additionally, in vitro and ex vivo autoradiographic studies revealed high unspecific binding which makes this ligand unsuitable for SPECT imaging.

Animals↗
PubMed2003

[Primary hyperparathyroidism with persistent hypercalcemia in pregnancy].

Parathyroidectomy is effective in avoiding complications of primary hyperparathyroidism (pHPT) during pregnancy, because in about 90% of cases, it is caused by parathyroid adenomas. We present a case of severe pHPT during pregnancy of unknown etiology and without detectable parathyroid adenoma so that surgery was not a therapeutic option. The patient was a 29-year-old gravida 1 who presented with pHPT at 11 weeks of gestation. Although her serum calcium levels were elevated throughout pregnancy (>3.05 mmol/l; reference range: 2.05-2.65), a vigorous premature infant was delivered at 35 weeks of gestation. The infant received calcium intravenously, vitamin D(3) orally and was fed with raw human milk (low phosphorus) to prevent hypocalcemia. The baby did not develop clinical signs of hypocalcemia. Her initial parathyroid hormone level was suppressed (1.1 pg/ml; reference range: 15-65) and was normal at the age of 8 weeks. She was discharged from hospital at 14 days of life. Her physical, cognitive and motor development was normal through infancy and early childhood. In conclusion, pHPT during pregnancy does not necessarily lead to fetal or neonatal morbidity or mortality.

Adult↗
PubMed2002

Respiratory mechanical unloading and proportional assist ventilation in infants.

UNLABELLED: Conventional patient-triggered ventilation attempts to synchronize the upstroke in ventilator pressure with the onset of spontaneous inspiration. Other parameters of the mechanical cycle such as the peak inspiratory pressure are preset by the clinician. They will be imposed on the infant regardless of the actual spontaneous respiratory drive. Proportional assist ventilation (PAV) and respiratory mechanical unloading of spontaneous breathing (RMU, resistive and elastic unloading) are based on fundamentally different concepts. In contrast to the conventional perception of the ventilator being a pump, RMU/PAV servo-controls the applied ventilator pressure continuously throughout each inspiration. These modalities proportionally enhance the effect on ventilation of each respiratory effort. They rely on rather than interfere with the subject's respiratory control system. The patient controls all variables of the respiratory pattern while the ventilator works fully enslaved as a proportional amplifier. Back-up conventional mechanical ventilation is initiated during episodes of hypoventilation and apnoea. The clinician sets the degree of the assist during RMU/PAV in terms of "gains". Selecting specific gains for the elastic and resistive unloading components allows the ventilator pressure waveform to be tailored to the individual degree of restrictive and obstructive pulmonary disease. This results in a reduction in the transpulmonary pressure cost of ventilation compared with conventional modes. CONCLUSION: Further studies on RMU/PAV are required to evaluate clinically important long-term outcome variables in infants and to determine whether the benefits outweigh potential drawbacks and the complexity involved in these new modes of mechanical ventilation.

Airway Resistance↗
PubMed2001

Analysis of the transcriptional program induced by Raf in epithelial cells.

Activation of the Raf/MAP kinase pathway is a critical event in tumorigenesis induced by RAS and other oncogenes, a major role of this signaling system being the regulation of cellular transcription factors. To address the contribution of MAP kinase mediated transcriptional changes to the transformed phenotype, we used an inducible form of Raf to analyze early changes in the transcription of some 6000 genes following activation of the kinase in a normal human breast epithelial cell line. Of the more than 120 significant changes in mRNA level detected, genes promoting cell proliferation, invasiveness, and angiogenesis featured prominently. Some of the most strongly induced genes encoded growth factors of the EGF family: Autocrine activation of the EGF receptor was shown to be responsible for the ability of Raf activation to protect these cells from apoptosis induced by detachment of cells from extracellular matrix (anoikis), which is a critical component of the transformed phenotype.

Apoptosis↗
PubMed2001

Prenatal diagnosis of congenital heart disease and neonatal outcome--a six years experience.

BACKGROUND: Prenatal diagnosis of congenital heart disease (CHD) is important for proper perinatal and neonatal management, as CHD occurs in approximately eight of 1000 live births. Antenatal detection of cardiac malformations is crucial as altered obstetric and neonatal management may be required and the neonate will benefit from delivery at a tertiary care center. METHODS: A retrospective comparison between pre- and postnatal diagnoses was accomplished. All fetal echocardiographic scans performed and CHD's detected postnatally between January 1994 and December 1999 by the department of obstetrics and gynecology and pediatric cardiology - Grosshadern, Munich University Hospital were reviewed. RESULTS: The incidence of CHD was 1.5% (116/ 7913). CHD was suspected by prenatal ultrasound in 57 fetuses. Postnatally, 116 congenital cardiac anomalies were diagnosed. Overall, the intrauterine detection rate was 38% (44/116). 72% (84) of the diagnosed anomalies were Septal Defects, 16% (19) disorders of the Atrioventricular Valves and 11% (13) Anomalies of the Great Vessels. In 10% (11) of fetuses chromosomal abnormalities were found. 8% (9) newborns suffered from congenital syndromes. In 55% (64) children were delivered preterm (<37 weeks of gestation). 5% (6) of the neonates required surgery within their first year of life. 28% (33) of children with CHD did not survive the first year of life. CONCLUSION: As the prenatal diagnosis is important for pre-, peri- and postnatal management, diagnostic accuracy is essential. Nevertheless, the accuracy of postnatal pediatric echo still exceeds that of the prenatal scan.

Adolescent↗
PubMed2001

Comparative anatomy of excretory organs in vestimentiferan tube worms (Pogonophora, Obturata).

In the past, the excretory systems of only few vestimentiferan species have been examined in detail. This study presents comparative data on eight species on the basis of histological serial sections. Ridgeia piscesae was studied by transmission electron microscopy. All species examined possess a central excretory organ consisting of numerous small branching and intertwined excretory tubules. These are connected to voluminous glandular excretory ducts that lead to the exterior by single or paired excretory pores located at the anterior end of the vestimentum. A comparative analysis shows differences among the species with regard to several features, such as the number of excretory pores, presence/absence of excretory grooves and papillae, position of the excretory organ relative to the brain, and the shape of the excretory ducts. Neither podocytes nor coelomoducts could be detected; therefore, there is no indication of the presence of metanephridia. The vestimentiferan excretory system shows some similarities with the design in Athecanephria (Pogonophora, Perviata) and a general resemblance to the design in sabellid polychaetes, even though in the latter metanephridia are clearly present.

Animals↗
PubMed2001

Exclusion of SOX9 as the testis determining factor in Ellobius lutescens: evidence for another testis determining gene besides SRY and SOX9.

In mammals the initiation of testis determination usually depends on the Y-chromosomal gene SRY. A few species, however, escape from this rule with a testis determination that is independent of SRY. The mole vole Ellobius lutescens is one of these species. It is not known how testis determination is initiated in this species but it has been suggested that a gene from the sex determination cascade usually acting downstream of SRY is mutated and has taken over the testis-determining function. At present SOX9 is the only candidate gene for which a testis-determining function in the absence of SRY has been observed. To test the hypothesis that testis differentiation in E. lutescens is initiated by SOX9, segregation analysis of SOX9 alleles was performed in an E. lutescens family. As there is no marker data available in this species we screened both Ellobius SOX9 introns for polymorphisms suitable for segregation studies. A biallelic polymorphism was found in the second intron of the SOX9 gene and analysis of this marker in the Ellobius family revealed an inheritance pattern completely independent of the sex of the animals. Thus, SOX9 can be excluded from being the testis-determining factor in E. lutescens. These results provide evidence for another possibly yet unknown gene besides SRY and SOX9 able to exert testis-determining function.

Alleles↗
PubMed2001

Improving treatment of guanidinoacetate methyltransferase deficiency: reduction of guanidinoacetic acid in body fluids by arginine restriction and ornithine supplementation.

Guanidinoacetate methyltransferase (GAMT) deficiency (McKusick 601240), an inborn error of creatine biosynthesis, is characterized by creatine depletion and accumulation of guanidinoacetate (GAA) in the brain. Treatment by oral creatine supplementation had no effect on the intractable seizures. Based on the possible role of GAA as an epileptogenic agent, we evaluated a dietary treatment with arginine restriction and ornithine supplementation in order to achieve reduction of GAA. In an 8-year-old Kurdish girl with GAMT deficiency arginine intake was restricted to 15 mg/kg/day (0.4 g natural protein/kg/day) and ornithine was supplemented with 100 mg/kg/day over a period of 14 months. The diet was enriched with 0.4 g/kg/day of arginine-free essential amino acid mixture and creatine treatment remained unchanged (1.1 g/kg/day). Guanidino compounds in blood, urine, and CSF were measured by means of cation-exchange chromatography. The combination of arginine restriction and ornithine supplementation led to a substantial and permanent decrease of arginine without disturbance of nitrogen detoxification. Formation of GAA was effectively reduced after 4 weeks of treatment and sustained thereafter. Biochemical effects were accompanied by a marked clinical improvement. Distinctly reduced epileptogenic activities in electroencephalography accompanied by almost complete disappearance of seizures demonstrates the positive effect of GAA reduction. This indicates for the first time that GAA may exert an important epileptogenic potential in man. Arginine restriction in combination with ornithine supplementation represents a new and rationale therapeutic approach in GAMT deficiency.

Amino Acid Metabolism, Inborn Errors↗