Desmopressin testing in haemophilia A patients and carriers: results of a multi centre survey.

INTRODUCTION: Desmopressin (DDAVP) testing (DT) in patients (pts) with haemophilia A (HA) and carriers (CHA) is up to now not standardized. This prompted us to evaluate results of DT carried out between 1996 and 2011 in centres of the Competence Network Haemorrhagic Diatheses East. PATIENTS AND METHOD: An increase of the factor VIII activity (FVIII) above 50% or at least the two fold of initial values within 120 min after DDAVP was defined as complete response (CR). Data from 80 patients (31 children, 49 adults) of whom 64 suffered from HA (sub-HA: n=48; mild: n=14; moderate: n=2) and 16 patients CHA were evaluated. RESULTS: In 34 patients DDAVP was given i.v. (dose range: 0.26-0.6 µg/kg body weight, mean: 0.33), in 31 intranasally (i.n. 300-600 µg) and in 15 s.c. (15-40 µg). The maximal FVIII increase was reached 60 min after DDAVP. For i.v. application the mean FVIII increase was 3.1-fold, for i.n. 2.1-fold and for s.c. 2.4-fold. A CR was detected in 71 patients, a non-response in 9. Mild side effects such as flush, headaches or nausea were observed in 11 patients (14%). CONCLUSION: For desmopressin testing in patients with haemophilia A and carriers i.v. application at 0.3 µg/kg body weight and the determination of FVIII before and 60 min after desmopressin infusion is recommended.

Entities and frequency of neonatal diabetes: data from the diabetes documentation and quality management system (DPV).

AIMS: The aim of this study was to elucidate the entities and the frequency of neonatal diabetes mellitus (NDM) in a large representative database for paediatric diabetes patients in Germany and Austria. METHODS: Based on the continuous diabetes data acquisition system for prospective surveillance (DPV), which includes 51,587 patients with onset of diabetes before the age of 18 years from 299 centres in Germany and Austria, we searched for patients with onset of diabetes mellitus in the first 6 months of life. RESULTS: Ninety patients were identified, comprising 0.17% of all paediatric cases in the DPV registry. This represented an incidence of approximately one case in 89,000 live births in Germany. A monogenic basis for NDM was established in 30 subjects (seven UPD6, 10 KCNJ11, seven ABCC8, two FOXP3, two PDX1, one INS, one EIF2AK3). Pancreatic hypoplasia or agenesis was reported in 10 patients and seven subjects were classified as having Type 1 diabetes by their centres. Transient neonatal diabetes (TNDM) accounted for approximately 10% of all cases with NDM. No aetiology was defined in 41 subjects, which may reflect incomplete genetic testing or novel genetic aetiologies. CONCLUSION: Based on a large database, we identified a higher rate of NDM in Germany than has been reported previously. Full molecular genetic testing should be performed in all patients diagnosed before 6 months of age.

Calorimetric observation of the melting of free water nanoparticles at cryogenic temperatures.

We present an experimental study of the thermodynamics of free, size-selected water cluster anions consisting of 48 and 118 molecules. The measured caloric curves of the clusters are bulklike at low temperatures but show a well-defined, particle-size specific transition at 93+/-3 K for (H2O)48- and 118+/-3 K for (H2O)118-. At the transition temperature the heat capacity strongly increases, which marks the onset of melting.

Melting-point depression by insoluble impurities: a finite size effect.

Melting-point depression by soluble impurities is an entropy-driven phenomenon. Studying partially oxidized free sodium nanoparticles, we found an additional mechanism, which is caused by insoluble impurities. Oxidization of sodium clusters with 135-192 atoms by a single oxygen molecule causes a melting-point depression of 17+/-6 K; additional oxygen amplifies the effect. This is in contrast to the behavior of bulk sodium, where the melting point does not change upon partial oxidization. First-principles density functional theory calculations reveal the interaction between the pure and the oxidized part of the cluster to be responsible for the effect. There is more structural freedom in a liquid cluster to optimize the interface between the two parts. This stabilizes the liquid phase and causes the observed, cluster-specific melting-point depression.

Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries.

AIMS/HYPOTHESIS: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome. METHODS: Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA(1c) was measured centrally. RESULTS: A total of 1,041 patients (age: 11.8 +/- 4.2 years; diabetes duration: 6.0 +/- 3.6 years; average CSII duration: 2.0 +/- 1.3 years; HbA(1c): 8.0 +/- 1.3% [means +/- SD]) participated. Glycaemic control was better in preschool (n = 142; 7.5 +/- 0.9%) and pre-adolescent (6-11 years, n = 321; 7.7 +/- 1.0%) children than in adolescent patients (12-18 years, n = 578; 8.3 +/- 1.4%). There was a significant negative correlation between HbA(1c) and daily bolus number, but not between HbA(1c) and total daily insulin dose. The use of <6.7 daily boluses was a significant predictor of an HbA(1c) level >7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively. CONCLUSIONS/INTERPRETATION: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c).

Shorter remission period in young versus older children with diabetes mellitus type 1.

BACKGROUND: The initial period of diabetes type 1 is of great importance, since early metabolic adjustment has profound impact on long term control. The majority of pediatric centers in Germany participate in a national quality initiative, providing longitudinal data for central analysis. PATIENTS: 104543 anonymous data sets were obtained from 6123 pediatric patients under 18 years who were treated in 157 pediatric centers and monitored for 36 months at the same center starting from diagnosis. RESULTS: Partial remission (insulin <0.5 U/kg/d and HbA1c < or = 7.0%) was present in 1992 children (32.5%) within the first 3 months after diagnosis. Remission phase lasted in average for 0.74 +/- 0.77 years and was significantly shorter in children below 10 years of age at onset of diabetes compared to the older patients. The remission period was significantly longer in boys, particularly in children under 10 years (p=0.0039). Multiple regression analysis showed a longer remission phase in children with pubertal diabetes onset. The children entering remission were younger, more often boys and had a lower initial HbA1c level. CONCLUSION: These data from a large multicenter group of children with diabetes type 1 emphasize the influence of gender, pubertal stage and age at manifestation on the amount of insulin required, and therefore the clinical remission, during the first three years of the disease.

Influence of energy and entropy on the melting of sodium clusters.

Energetic and entropic influences on the melting temperatures of size selected sodium clusters are experimentally separated. It is shown that the energetic difference between solid and liquid is the leading influence for the still puzzling features in the size dependence of sodium melting points. Additionally, this energy difference decreases towards smaller cluster sizes and causes steplike melting phase transitions to vanish. The entropy difference between solid and liquid has been found to be strongly correlated with the energy and causes a pronounced damping of the energetic influences.

Caloric curve across the liquid-to-gas change for sodium clusters.

The caloric curve for Na(139)(+) has been measured from 100 K up to the temperature where the clusters are boiling hot and spontaneously emit atoms. In this limit the clusters form an evaporative ensemble, the temperature and energy of which have been determined. As the caloric curve of an atomic gas with a finite number of atoms is known, one can construct the caloric curve for this finite system below and above the boiling point. A conjecture is made on how to link the evaporative ensemble temperature of the free cluster in vacuum to the boiling temperature of a finite system at a given pressure. This allows one to determine the enthalpy of vaporization at the phase transition of the finite system.

Harmonics generation in electron-ion collisions in a short laser pulse.

Anomalously high generation efficiency of coherent higher field harmonics in collisions between oppositely charged particles in the field of femtosecond lasers is predicted. This is based on rigorous numerical solutions of a quantum kinetic equation for dense laser plasmas that overcomes limitations of previous investigations.

Physical effects of heliox versus oxygen on measurements of functional residual capacity by the nitrogen washout technique in small lung volumes: a model study.

Measurements of functional residual capacity (FRC) by the nitrogen (N(2)) washout technique yield low N(2) signals in neonates and preterm infants, especially when they are on high fractions of inspired oxygen (FiO(2)). Thus, recorded values often lie in the low range of detectability. We hypothesized that using heliox instead of oxygen as a washout gas would affect the electric discharge conditions of N(2) molecules in a standard UV analyzer and thus yield higher N(2) signals. We performed three laboratory experiments using conditions similar to those in neonates with pulmonary disease, reproducing different initial FiO(2) values and very small lung volumes. Standard calibration procedures with physical models between 13.5-87 mL using a calibration syringe and purpose-built small calibration cylinders were carried out, and washout gas was either pure oxygen (as is general practice) or heliox at different ratios. We observed that the calibration line with heliox was shifted upwards and the slope was increased, depending on helium concentration and initial FiO(2). Since this effect was dose-dependent with respect to the proportion of helium in the washout gas, this strongly suggests a physical process elicited by the noble gas helium. We conclude that the heliox wash-out modification may help to increase the accuracy of FRC measurements and thus may enable studies of smaller patients or patients on high inspired FiO(2).

Negative heat capacity for a cluster of 147 sodium atoms.

There exists a surprising theoretical prediction for a small system: its microcanonical heat capacity can become negative. An increase of energy can-under certain conditions-lead to a lower temperature. Here we present experimental evidence that a cluster containing exactly 147 sodium atoms does indeed have a negative microcanonical heat capacity near its solid to liquid transition.