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Biomedical subjects

Andreas Schulze

Publications and source records attributed to Andreas Schulze.

34 records · Page 2Linked to original sources
PubMed2003

Maternal and neonatal morbidity of emergency caesarean sections with a decision-to-delivery interval under 30 minutes: evidence from 10 years.

PURPOSE: The purpose was to investigate the decision-to-delivery interval for emergency caesarean section and to compare the perioperative maternal and neonatal morbidity to that of intrapartum non-emergent caesarean section. MATERIALS AND METHODS: A cohort study was designed evaluating 109 women undergoing 'crash' emergency caesarean section and 109 controls from 1988 to 1997 in a University hospital. All emergency caesarean sections were performed in the delivery room. Controls were matched by gestational age. Retrospective collection of data relating to indication, maternal and neonatal outcome of both groups was conducted. Time intervals between decision to deliver and actual delivery were collected for all emergency deliveries. RESULTS: The emergency caesarean section cohort represented a high risk group with a mean gestational age of 34.8 weeks and a high number of patients with preterm labour (29.3%). All 109 emergency caesarean sections were achieved within a decision-to-delivery time of 30 min. Severe maternal haemorrhage was significantly higher mainly because of underlying obstetrical complications such as placenta praevia, placental abruption, and others resulting in a blood transfusion rate of 10.1%. Procedure related and infectious maternal morbidity, however, was not significantly increased. All women undergoing the emergency procedure received perioperative antibioprophylaxis. Mean umbilical arterial blood pH and Apgar scores were significantly lower in infants delivered by emergency caesarean section but there was no difference in the admission to the NICU. CONCLUSIONS: Emergency caesarean section performed in the delivery room may result in a decision-to-delivery time of less than 30 min without detrimental perioperative effects on mother or infant.

Adult↗
PubMed2003

Effect of body temperature on the pattern of spontaneous breathing in extremely low birth weight infants supported by proportional assist ventilation.

The optimum body temperature for infants <1000 g is unknown. We investigated body temperature effects on spontaneous breathing using proportional assist ventilation (PAV), because this mode supports spontaneous breathing such that all breathing pattern variables remain controlled by the infant. Minute volume (MV), respiratory rate (RR), tidal volume (Vt), incidence and duration of respiratory pauses, arterial oxygen desaturations <85%, and arterial Pco2 levels will remain unaffected by targeting core body temperature to 36.1-36.5 degrees C (low normal range) versus 37.7-37.9 degrees C (upper normal). Twenty infants (mean +/- SD: birth weight, 696 +/- 155 g; gestational age, 25 +/- 1 wk; age, 5 +/- 3 d) who were supported by PAV were exposed to each target temperature range on 2 consecutive days in four 2-h intervals for a total of 8 h with the sequence of the temperature ranges randomized. Core body temperature was 36.5 +/- 0.2 degrees C and 37.9 +/- 0.2 degrees C in the two conditions. MV was 291 and 314 mL. min-1. kg-1, respectively (7% difference; p < 0.001) as a result of a difference in RR (8%; p < 0.001). The infants maintained their blood CO2 levels and Vt (5.25 +/- 0.6 versus 5.19 +/- 0.6 mL/kg). Incidence and duration of respiratory pauses were not different between conditions. Extremely immature infants who are supported by PAV modify their spontaneous breathing in response to changes in thermal environment such that Pco2 levels are appropriately maintained early in postnatal life. This response pattern occurred consistently and is currently of uncertain clinical significance.

Behavior↗
PubMed2003

Lack of creatine in muscle and brain in an adult with GAMT deficiency.

Guanidinoacetate methyltransferase deficiency, which so far has been exclusively detected in children, was diagnosed in a 26-year-old man. The full-blown spectrum of clinical symptoms already had been present since infancy without progression of symptoms during adolescence. Cranial magnetic resonance imaging showed normal findings. Ophthalmological examination showed no retinal changes. Besides creatine deficiency in the brain, a distinct lack of phosphocreatine in skeletal muscle was proved by (31)P magnetic resonance spectroscopy. Creatine substitution combined with a guanidinoacetate-lowering diet introduced first at the age of 26 years was shown to be effective by an impressive improvement of epileptic seizures, mental capabilities, and general behavior and by normalization of the (31)P spectrum in the skeletal muscle.

Adult↗
PubMed2003

Accurate measurement of free carnitine in dried blood spots by isotope-dilution electrospray tandem mass spectrometry without butylation.

BACKGROUND: To test the feasibility of free carnitine (FC) determination in dried blood spot specimens (DBS) by stable isotope-dilution electrospray-ionisation tandem mass spectrometry (MS/MS). METHODS: The MS/MS method established for newborn screening, measuring acylcarnitines by positive precursor ion scan of m/z 85 in DBS, was adapted by omitting the butylation and heating step during sample preparation. FC measurement in DBS by this non-butylating MS/MS assay was compared with the butylating MS/MS method and the spectrophotometric Cobas method. RESULTS: FC measurement by the non-butylating MS/MS method meets the demands for a bioanalytical microassay with respect to linearity, detection limit (LOD), accuracy, and precision. Formation of FC was 0-1% and 1-4% in liquid samples and in DBS by the non-butylating MS/MS method, while 3-10% and 8-16% by the butylating method, respectively. Acid-catalysed hydrolysis (butanolysis) in liquid samples was higher for short-chain acylcarnitines (acetyl- and propionylcarnitine). Hydrolysis in DBS was more pronounced for long-chain acylcarnitines. FC concentrations in healthy newborns without butylation were 35% lower than those measured by the established newborn screening assay. CONCLUSIONS: The non-butylating MS/MS assay provides a simple and accurate method for FC determination in DBS and represents a trivial but important adaptation of a method already used in many laboratories.

Calibration↗
PubMed2003

Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.

OBJECTIVE: The aims of this study were to determine the impact of expanded newborn screening using tandem mass spectrometry (MS/MS) on the overall detection rate of inborn errors of metabolism in Germany and to assess the outcome for the patients that were diagnosed. METHODS: During the period of study, 250,000 neonates in a German population were investigated for 23 inborn errors of metabolism by electrospray ionization-MS/MS. The overall value of the screening program was estimated by 1) complete ascertainment of all positive tests; 2) definite assignment of all diagnoses including reconfirmation at 12 months; and 3) clinical follow-up of all detected patients in an overall interval of 42 months. The mean observation period was 13.5 months per child. RESULTS: In 106 newborns, confirmed inborn errors of metabolism were found. The disorders were classified as 50 classic forms and 56 variants. A total of 825 tests (0.33%) were false-positives. Seventy of the 106 newborns with confirmed disorders were judged to require treatment. Six children developed symptoms despite treatment. Three children had died. Among 9 children who became symptomatic before report of the results of screening, in 6 the diagnosis had been made in advance of the screening report. In evaluation of the screening program, 61 of the 106 identified children (58% of true-positives, or 1 of 4100 healthy newborns) were judged to have benefited from screening and treatment, because the diagnosis had not been made before screening. None of these infants had died and none developed psychomotor retardation or metabolic crisis during the follow-up period. CONCLUSIONS: The screening by MS/MS for up to 23 additional disorders has approximately doubled the detection rate compared with that achieved by the conventional methods used in Germany. This strategy represents valuable preventive medicine by enabling diagnosis and treatment before the onset of symptoms.

Acyl-CoA Dehydrogenase↗
PubMed2003

Creatine deficiency syndromes.

Since the first description of a creatine deficiency syndrome, the guanidinoacetate methyltransferase (GAMT) deficiency, in 1994, the two further suspected creatine deficiency syndromes--the creatine transporter (CrT1) defect and the arginine:glycine amidinotransferase (AGAT) deficiency were disclosed. GAMT and AGAT deficiency have autosomal-recessive traits, whereas the CrT1 defect is a X-linked disorder. All patients reveal developmental delay/regression, mental retardation, and severe disturbance of their expressive and cognitive speech. The common feature of all creatine deficiency syndromes is the severe depletion of creatine/phosphocreatine in the brain. Only the GAMT deficiency is in addition characterized by accumulation of guanidinoacetic acid in brain and body fluids. Guanidinoacetic acid seems to be responsible for intractable seizures and the movement disorder, both exclusively found in GAMT deficiency. Treatment with oral creatine supplementation is in part successful in GAMT and AGAT deficiency, whereas in CrT1 defect it is not able to replenish creatine in the brain. Treatment of combined arginine restriction and ornithine substitution in GAMT deficiency is capable to decrease guanidinoacetic acid permanently and improves the clinical outcome. The lack of the creatine/phosphocreatine signal in the patient's brain by means of in vivo proton magnetic resonance spectroscopy is the common finding and the diagnostic clue in all three diseases. In AGAT deficiency guanidinoacetic acid is decreased, whereas creatine in blood was found to be normal. On the other hand the CrT1 defect is characterized by an increased concentration of creatine in blood and urine whereas guanidinoacetic acid concentration is normal. The increasing number of patients detected very recently suffering from a creatine deficiency syndrome and the unfavorable outcome highlights the need of further attempts in early recognition of affected individuals and in optimizing its treatment. The study of creatine deficiency syndromes and their comparative consideration contributes to the better understanding of the pathophysiological role of creatine and other guanidino compounds in man.

Administration, Oral↗
PubMed2002

Staphylococcal scalded skin syndrome related to an exfoliative toxin A- and B-producing strain in preterm infants.

UNLABELLED: A previously well, spontaneously breathing premature infant (gestational age 25 weeks, birth weight 364 g, age 74 days) developed staphylococcal scalded skin syndrome (SSSS). A methicillin-sensitive strain of Staphylococcus aureus producing exfoliative toxins A and B (ETA, ETB) was isolated from a gastric aspirate and a pharyngeal swab. The disease recurred with a milder clinical picture 4 weeks later in the same patient while under steroid treatment. Cultures obtained from conjunctiva and pharynx were again positive for S. aureus. A second premature infant in an adjacent ward developed SSSS 2 weeks after the recurrence in the first patient. No other cases were observed thereafter. A total of 25 individuals who had contact with the first patient were screened for staphylococcal colonisation. S.aureus was isolated from the posterior part of the nasal cavity in 8 of the 25 contacts. These strains and the strain of the first patient were evaluated by PCR for the presence of genes encoding ETA and ETB. Expression of toxins was confirmed by gel electrophoresis and Western blot analysis. Purified toxins were injected into newborn mice to confirm toxin activity. Besides the strain isolated from the first patient, only one isolate from the medical staff was positive for the genes encoding ETA and ETB. CONCLUSION: the carrier of this strain had contact with both patients, suggesting that this individual was the vector between the two patients but not necessarily the source of the original infection. Strict infection control measures were implemented and no further spread of the disease occurred.

Blotting, Western↗
PubMed2002

A method for quantitative acylcarnitine profiling in human skin fibroblasts using unlabelled palmitic acid: diagnosis of fatty acid oxidation disorders and differentiation between biochemical phenotypes of MCAD deficiency.

Inherited disorders of fatty acid oxidation are a group of acute life-threatening but treatable disorders, clinically complicated by severe hypoketotic hypoglycemia precipitated by prolonged fasting. Among them, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is by far the most frequent disorder. Here we report a modified method for quantitative acylcarnitine profiling by electrospray ionisation-tandem mass spectrometry (ESI-MS-MS) in human skin fibroblasts using unlabelled palmitic acid as substrate. The reliability of this method was tested in cultured skin fibroblasts from previously diagnosed patients with specific carnitine cycle and fatty acid beta-oxidation defects. Furthermore, acylcarnitine profiling was investigated in fibroblasts and dried blood spots from patients with different variants of MCAD deficiency. ESI-MS-MS-based investigation of cultured skin fibroblasts from patients with disorders of fatty acid oxidation revealed a pathognomonic acylcarnitine profiling. In addition, this method delineated different variants of MCAD deficiency, i.e. mild and classical. The octanoylcarnitine (C8)-to-decanoylcarnitine (C10) and C8-to-acetylcarnitine (C2) ratios were the most specific markers to differentiate mild and classical forms of MCAD deficiency in fibroblasts. Similar results were obtained by quantitative acylcarnitine profiling in dried blood spots. In conclusion, this novel technique is a powerful tool for the investigation of fatty acid oxidation disorders under standardized conditions in fibroblasts.

Acyl-CoA Dehydrogenase↗
PubMed2002

Increased levels of antimicrobial peptides in tracheal aspirates of newborn infants during infection.

Pneumonia and systemic infection are common in premature infants. The antimicrobial peptides human beta-defensin 1 and 2 (hBD-1 and hBD-2) and the cathelicidin LL-37/hCAP-18 are effector molecules of the innate respiratory immune system. It is unknown whether these host defense substances are produced in the respiratory tract of newborns. Concentrations of these peptides were determined in tracheal aspirates of mechanically ventilated newborn infants. All three antimicrobial peptides could be detected in airway lining fluid with equivalent levels in term and preterm newborns. Concentrations of antimicrobial peptides correlated with each other and with levels of interleukin-8 and tumor necrosis factor-alpha in the bronchoalveolar lavage fluid. Pulmonary or systemic infections were associated with significantly increased concentrations of LL-37, hBD-1, and hBD-2. Western blotting detected mature peptides in the lavage fluid. In conclusion, mucosal antimicrobial peptides are present in lung secretions of premature and mature newborns. The molecules are upregulated in response to infection and inflammation and probably represent effector molecules of the respiratory defense system.

Antimicrobial Cationic Peptides↗
PubMed2002

Evaluation of 6-year application of the enzymatic colorimetric phenylalanine assay in the setting of neonatal screening for phenylketonuria.

BACKGROUND: Most reports on phenylketonuria (PKU) screening focused solely on the result of the initial investigation of the neonatal screening sample. The aim of this study was to evaluate an enzymatic phenylalanine (Phe) determination in the whole context spanning from the initial investigation over the recall period, up to the confirmation or exclusion of the disease. METHODS: Phe of dried blood spot specimens was analysed colorimetrically in a microtitre-plate assay based on the L-phenylalanine dehydrogenase reaction coupled with an intermediate electron acceptor system. This assay was evaluated for analytical variables and for neonatal PKU screening in a total number of 423,773 neonates during a 6-year period. RESULTS: Method validation with respect to linearity, precision (within-run CVs 3.4-4.2%, between-run CVs 6.2-10.4%), and accuracy fulfilled all requirements for a screening method. Mean Phe (+/-SD) of 130,000 healthy neonates was 84 (+/-22) micromol/l with a cut-off point (mean+3 SD) of 150 micromol/l. From 423,773 neonates, hyperphenylalaninemia was confirmed in 155 cases and further differentiated into PKU (41 cases, 27%), BH(4) deficiency (3, 2%), non-PKU HPA (67, 43%), transient neonatal HPA (28, 18%), and secondary HPA (16, 10%). The number of false-positives (recall-rate) was 0.23%, and no false-negatives were noted. CONCLUSIONS: Detailed studies over a period of 6 years including more than 400,000 neonates clearly show that the enzymatic assay is a reliable and sensitive method for neonatal screening of PKU. The proven prevalence of non-PKU HPA in the German population disclosed by the assay was twice as high as compared to the "Guthrie test" used previously. The growing use and application of tandem mass spectrometry in neonatal screening will not derogate the usefulness of the enzymatic assay in PKU screening in the foreseeable future. Careful analysis of our screening results and monitoring of all pathological samples resulted in an evidence-based flow chart for a rational PKU screening.

Amino Acid Metabolism, Inborn Errors↗
PubMed2002

Health implications of creatine: can oral creatine supplementation protect against neurological and atherosclerotic disease?

Major achievements made over the last several years have highlighted the important roles of creatine and the creatine kinase reaction in health and disease. Inborn errors of metabolism have been identified in the three main steps involved in creatine metabolism: arginine:glycine amidinotransferase (AGAT), S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase (GAMT), and the creatine transporter. All these diseases are characterized by a lack of creatine and phosphorylcreatine in the brain, and by (severe) mental retardation. Similarly, knockout mice lacking the brain cytosolic and mitochondrial isoenzymes of creatine kinase displayed a slightly increased creatine concentration, but no phosphorylcreatine in the brain. These mice revealed decreased weight gain and reduced life expectancy, disturbed fat metabolism, behavioral abnormalities and impaired learning capacity. Oral creatine supplementation improved the clinical symptoms in both AGAT and GAMT deficiency, but not in creatine transporter deficiency. In addition, creatine supplementation displayed neuroprotective effects in several animal models of neurological disease, such as Huntington's disease, Parkinson's disease, or amyotrophic lateral sclerosis. All these findings pinpoint to a close correlation between the functional capacity of the creatine kinase/phosphorylcreatine/creatine system and proper brain function. They also offer a starting-point for novel means of delaying neurodegenerative disease, and/or for strengthening memory function and intellectual capabilities.Finally, creatine biosynthesis has been postulated as a major effector of homocysteine concentration in the plasma, which has been identified as an independent graded risk factor for atherosclerotic disease. By decreasing homocysteine production, oral creatine supplementation may, thus, also lower the risk for developing, e.g., coronary heart disease or cerebrovascular disease. Although compelling, these results require further confirmation in clinical studies in humans, together with a thorough evaluation of the safety of oral creatine supplementation.

Administration, Oral↗
PubMed2002

Respiratory gas conditioning in infants with an artificial airway.

There is a strong physiological rationale for delivering the inspiratory gas at or close to core body temperature and saturated with water vapour to infants with an artificial airway undergoing long-term mechanical ventilatory assistance. Cascade humidifiers with heated wire ventilatory circuitry may achieve this goal safely. Whenever saturated air leaves the humidifier chamber at 37 degrees C and condensate accumulates in the circuit, the gas loses humidity and acquires the potential to dry airway secretions near the tip of the endotracheal tube. Heat and moisture exchangers and hygroscopic condenser humidifiers with or without bacterial filters have become available for neonates. They can provide sufficient moisture output for short-term ventilation without excessive additional dead space or flow-resistive load for term infants. Their safety and efficacy for very low birthweight infants and for long-term mechanical ventilation has not been established conclusively. A broader application of these inexpensive and simple devices is likely to occur with further design improvements. When heated humidifiers are appropriately applied, water or normal saline aerosol application offers no additional significant advantage in terms of inspiratory gas conditioning and may impose a water overload on the airway or even systemically. Although airway irrigation by periodic bolus instillation of normal saline solution prior to suctioning procedures is widely practised in neonatology, virtually no data exist on its safety and efficacy when used with appropriately humidified inspired gas. There is no evidence that conditioning of inspired gas to core body temperature and full water vapour saturation may promote nosocomial respiratory infections.

Equipment Design↗
PubMed2002

Acylcarnitine profiles of preterm infants over the first four weeks of life.

Measurement of free carnitine and acylcarnitines allows the detection of several inborn errors of metabolism in neonatal screening. Because available data for premature infants is limited, we studied longitudinal changes in acylcarnitine profiles of full-term and preterm neonates over the first 4 weeks of life. One hundred twenty infants were divided into four groups of 30: A, gestational age 22 to 27 wk; B, 28 to 31 wk; C, 32 to 36 wk; and D, 37 to 41 wk. Blood samples spotted on a Guthrie card were taken on days 5 and 28. Additional specimens (groups A and B only) were collected on days 1, 3, 7, and 14. Carnitine and its acyl esters were detected by looking for the precursor ions of m/z = 85 using a PE Sciex API 365 electrospray ionization tandem mass spectrometer. Concentrations of free carnitine and most acylcarnitines were significantly higher in group A compared with group D postnatally. Groups B and C displayed intermediate values. Carnitine levels in infants from group A and B decreased steadily from day 1 to day 7, and recovered up to day 14 in group B only. On day 28 carnitine concentrations had further decreased in group A, while reaching postnatal levels again in group B. Postnatal carnitine levels are higher in very immature preterm infants compared with full-term infants, but become lower on day 28. However, the commonly used metabolite ratios should still allow the detection of inborn errors of metabolism.

Carnitine↗
PubMedDate not supplied

Resuscitation of newborn infants with 100% oxygen or air: a systematic review and meta-analysis.

BACKGROUND: International consensus statements for resuscitation of newborn infants recommend provision of 100% oxygen with positive pressure if assisted ventilation is required. However, 100% oxygen exacerbates reperfusion injury in animals and reduces cerebral perfusion in newborn babies. We aimed to establish whether resuscitation with air decreased mortality or neurological disability in newborn infants compared with 100% oxygen. METHODS: We did a systematic review and meta-analysis of trials that compared resuscitation with air versus 100% oxygen, using the methods of the Cochrane Collaboration. We combined data for similar outcomes in the analysis where appropriate, using a fixed-effects model. FINDINGS: Five trials (two masked and three unmasked), consisting of 1302 newborn infants, fulfilled the inclusion criteria. Most babies were born at or near term in developing countries. In the three unmasked studies, infants resuscitated with room air who remained cyanotic and bradycardic were switched to 100% oxygen at 90 s. The masked studies allowed crossover to the other gas during the first minutes of life. Although no individual trial showed a difference in mortality, the pooled analysis showed a significant benefit for infants resuscitated with air (relative risk 0.71 [95% CI 0.54 to 0.94], risk difference -0.05 [-0.08 to -0.01]). The effect on long-term development could not be reliably determined because of methodological limitations in the one study that followed up infants beyond 12 months of age. INTERPRETATION: For term and near-term infants, we can reasonably conclude that air should be used initially, with oxygen as backup if initial resuscitation fails. The effect of intermediate concentrations of oxygen at resuscitation needs to be investigated. Future trials should include and stratify for premature infants.

Air↗
PubMedDate not supplied

Multifetal gestation--maternal and perinatal outcome of 112 pregnancies.

PURPOSE: Multifetal pregnancy reduction is a widespread "therapy" to diminish the risk of prematurity and adverse outcome for the survivors in higher order multiple gestation. The aim of our study was to determine the maternal and neonatal outcome of multifetal pregnancies under a conservative pregnancy management. STUDY DESIGN: A retrospective review of 112 multifetal pregnancies is presented. All higher order multiple pregnancies delivered after 25 weeks of gestation and managed at a single institution between 1982 and 1999 are included. RESULTS: Triplets, quadruplets and quintuplets were delivered at a mean gestational age of 31 + 5, 29 + 5 and 28 + 4 weeks, respectively. The perinatal mortality was 14 for triplets and 36 for quadruplets. No quintuplet died in the perinatal period. Respiratory distress syndrome occurred in 23% of triplets, 65% of quadruplets and 75% of quintuplets, intracranial hemorrhage was diagnosed in 14% of triplets, 15% of quadruplets and 10% of quintuplets and retinopathy of prematurity was found in 10% of triplets, 9% of quadruplets and 25% of quintuplets. DISCUSSION: Despite a low neonatal mortality, morbidity of higher order multiple gestations remains significant. Mortality and morbidity are related to preterm delivery but do not exceed the rates of singletons or twins of an identical gestational age. Favorable prognostic landmarks are a gestational age >30 weeks and a number of fetuses per pregnancy < or =4. CONCLUSION: The risks of multifetal pregnancies are significant. Therefore, evidence-based counseling of couples seeking treatment for infertility and prevention of higher order multiple pregnancies through the prudent use of reproductive techniques attains paramount importance.

Delivery, Obstetric↗