[Accidents in children and adolescents. Analysis of the accident event]. / Unfälle von Kindern und Jugendlichen. Analyse des Unfallgeschehens.

BACKGROUND: Accidents are the most frequent cause of death in children and adolescents. The aim of this study was to determine factors, which affect injury severity and to compare the absolute number of accidents with exposition data. PATIENT AND METHODS: From 1 January 1999 to 31 December 2001 a school survey of 2325 pupils was carried out. The 3645 accidents sustained by children and adolescents aged between 6 and 17 years treated at the surgical emergency department of the University Hospital Dresden were analyzed. RESULTS: Of the 3645 patients, 620 (17%) were admitted to hospital and 3025 (83%) were treated as outpatients. The most frequent diagnosis of the hospitalized patients was commotio cerebri; 83% of 36 severely injured patients had a head injury. 55.5% (297 of 536) of children between 6 and 9 years were using a protective helmet. In contrast only 14% of adolescents carried a protective helmet. None of 50 injured bicycle drivers with helmet had an AIS for head injuries >2. Twenty-for of 233 injured bicycle drivers without helmet had an AIS for head injuries >2. CONCLUSIONS: Head injuries are the main cause of hospitalization in traumatized children and adolescents. However, the use of a protective helmet becomes significantly less frequent with increasing age.

[Evolution of a quality assurance programme for physiotherapy schools - results of the first quality inspections]. / Entwicklung eines Qualitätssicherungsprogramms für Physiotherapieschulen - Ergebnisse der ersten Qualitätsprüfungen.

In cooperation with the Hochrhein-Institute for Research in Rehabilitation (HRI), the Association for Assuring the Quality of Education in Physiotherapy Schools in Germany (ISQ) has developed a quality assurance programme for physiotherapy schools. It aims at assessing the quality of physiotherapy schools in Germany, and to award a quality seal based on compliance with defined criteria. First, a catalogue of quality features and criteria relevant for education in physiotherapy was developed. It is based on the analysis of questionnaires that had been sent to all German physiotherapy schools, to selected physiotherapists and leading physiotherapists in hospitals, to competent federal authorities, and to three school-classes with group discussions. The persons addressed named 360 different quality features. They were collected in a catalogue, revised in a multi-stage Delphi procedure, and approved consensually. The final criteria were transformed into basic quality requirements, and formulated as a check-list. Assessment of the quality features is carried out by trained visitors. In addition, the satisfaction of students is assessed with a questionnaire. The results of the interviews and the questionnaires are fed back to the schools in a quality report. Schools meeting all basic quality requirements are awarded the seal of quality. The seal is valid for three years. Since January 2003, this procedure is available for all schools in Germany. Until September 2002, a pretest of visitations and student questionnaires had been carried out with 31 member schools of the ISQ; according to the resulting quality reports, none of these schools would instantly be awarded the quality seal. In all, more than half of the schools do not meet 10 of the 42 basic criteria. Fundamental deficiencies have been found in the documentation pertaining to supervision of practical training. In terms of training, further training and professional development of their teachers and associated professors, needs for improvement could be shown in more than 66 % of all visited schools. Only 9 of 31 schools could produce a written syllabus. Additionally, the requirements of teachers conferences and equipment of libraries were not met by the majority. A general problem among the schools is inadequate documentation in many fields.

Epidermal growth factor receptor agonists increase expression of glutamate transporter GLT-1 in astrocytes through pathways dependent on phosphatidylinositol 3-kinase and transcription factor NF-kappaB.

The glial glutamate transporter GLT-1 may be the predominant Na(+)-dependent glutamate transporter in forebrain. Expression of GLT-1 correlates with astrocyte maturation in vivo and increases during synaptogenesis. In astrocyte cultures, GLT-1 expression parallels differentiation induced by cAMP analogs or by coculturing with neurons. Molecule(s) secreted by neuronal cultures contribute to this induction of GLT-1, but little is known about the signaling pathways mediating this regulation. In the present study, we determined whether growth factors previously implicated in astrocyte differentiation regulate GLT-1 expression. Of the six growth factors tested, two [epidermal growth factor (EGF) and transforming growth factor-alpha] induced expression of GLT-1 protein in cultured astrocytes. Induction of GLT-1 protein was accompanied by an increase in mRNA and in the V(max) for Na(+)-dependent glutamate transport activity. The effects of dibutyryl-cAMP and EGF were additive but were independently blocked by inhibitors of protein kinase A or protein tyrosine kinases, respectively. The induction of GLT-1 in both EGF- and dibutyryl-cAMP-treated astrocytes was blocked by inhibitors targeting phosphatidylinositol 3-kinase (PI3K) or the nuclear transcription factor-kappaB. Furthermore, transient transfection of astrocyte cultures with a constitutively active PI3K construct was sufficient to induce expression of GLT-1. These data suggest that independent but converging pathways mediate expression of GLT-1. Although an EGF receptor-specific antagonist did not block the effects of neuron-conditioned medium, the induction of GLT-1 by neuron-conditioned medium was completely abolished by inhibition of PI3K or nuclear factor-kappaB. EGF also increased expression of GLT-1 in spinal cord organotypic cultures. Together, these data suggest that activation of specific signaling pathways with EGF-like molecules may provide a novel approach for limiting excitotoxic brain injury.

Regulation of the glial Na+-dependent glutamate transporters by cyclic AMP analogs and neurons.

Sodium-dependent transport into astrocytes is critical for maintaining the extracellular concentrations of glutamate below toxic levels in the central nervous system. In this study, the expression of the glial glutamate transporters GLT-1 and GLAST was studied in primary cultures derived from cortical tissue. In primary astrocytes, GLAST protein levels were approximately one half of those observed in cortical tissue, but GLT-1 protein was present at very low levels compared with cortical tissue. Maintenance of these astrocytes in medium supplemented with dibutyryl-cAMP (dbcAMP) caused a dramatic change in cell morphology, increased GLT-1 and GLAST mRNA levels approximately 5-fold, increased GLAST protein approximately 2-fold, and increased GLT-1 protein >/=8-20-fold. These increases in protein expression were accompanied by 2-fold increases in the Vmax and Km values for Na+-dependent L-[3H]glutamate transport activity. Although GLT-1 is sensitive to inhibition by dihydrokainate in heterologous expression systems, no dihydrokainate sensitivity was observed in astrocyte cultures that expressed GLT-1. Biotinylation with a membrane-impermeant reagent, separation of the biotinylated/cell surface proteins, and subsequent Western blotting demonstrated that both GLT-1 and GLAST were present at the cell surface. Coculturing of astrocytes with neurons also induced expression of GLT-1, which colocalized with the glial specific marker, glial fibrillary acidic protein. Neurons induced a small increase in GLAST protein. Several studies were performed to examine the mechanism by which neurons regulate expression of the glial transporters. Three different protein kinase A (PKA) antagonists did not block the effect of neurons on glial expression of GLT-1 protein, but the addition of dbcAMP to mixed cultures of neurons and astrocytes did not cause GLT-1 protein to increase further. This suggests that neurons do not regulate GLT-1 by activation of PKA but that neurons and dbcAMP regulate GLT-1 protein through convergent pathways. As was observed with GLT-1, the increases in GLAST protein observed in cocultures were not blocked by PKA antagonists, but unlike GLT-1, the addition of dbcAMP to mixed cultures of neurons and astrocytes caused GLAST protein to increase approximately 2-fold. Neurons separated from astrocytes with a semipermeable membrane increased GLT-1 protein, indicating that the effect of neurons was mediated by a diffusible molecule. Treatment of cocultures with high concentrations of either N-methyl-D-aspartate or glutamate killed the neurons, caused GLT-1 protein to decrease, and caused GLAST protein to increase. These studies suggest that GLT-1 and GLAST protein are regulated independently in astrocyte cultures and that a diffusible molecule secreted by neurons induces expression of GLT-1 in astrocytes.

Elderly drivers in Germany--fitness and driving behavior.

During the period between 1985 and 2000 the number of elderly people (65 years and older) holding a driver's licence will probably double in Germany. Under the broadly accepted assumption that the elderly drive less safely than other age groups, it is suspected that this will negatively affect traffic safety. The central topic of the study concerns the results of driving tests with 80 elderly drivers (60-82 years old), compared with a reference group of 30 middle-aged motorists (40-50 years), and their relation to laboratory performance data. In the laboratory marked differences were found concerning visual acuity by daylight (even when deficiencies were corrected by visual aids) and in the dark, performance in a traffic-related tachistoscopic perception test, and notably in the amount of time needed in tracking and reaction tests. The performance of elderly drivers proved worse in all of these laboratory tasks. On the other hand, in driving tests in the overwhelming number of traffic situations the elderly did not differ unfavorably from the middle-aged drivers. Possible explanations for these findings are considered.

Increase in plasma total and lipoprotein cholesterol during incubation of whole blood samples at 37 degrees C--influence of LCAT inhibitors.

Incubation of whole blood samples at 37 degrees C caused a time-dependent increase in plasma cholesterol concentrations. In samples from 40 fasting healthy males, plasma cholesterol rose by 13.6 +/- 3% during 24 h (P less than 0.001). Changes in cholesterol concentrations were found in both the HDL fraction and the VLDL/LDL fraction. The increase in lipoprotein cholesterol concentrations correlated positively with the initial levels of HDL cholesterol and apo A-I; and with the original levels of VLDL/LDL cholesterol, apo B and triglycerides. The increase in plasma total cholesterol was not related to the HDL cholesterol and apo A-I concentrations. It was more pronounced in samples with elevated plasma concentrations of total cholesterol, VLDL/LDL cholesterol, apo B and triglycerides. The elevation in plasma total cholesterol resulted from an increase in cholesteryl esters, whereas free cholesterol decreased. After LCAT inhibition no changes in total, free and esterified cholesterol were observed. Therefore, increase in plasma cholesterol seems to represent a LCAT-dependent cholesterol transport out of blood cells.

[Empirical studies on the performance of elderly automobile drivers]. / Empirische Untersuchungen zur Leistungsfähigkeit älterer Kraftfahrer.

Before the year 2000 the number of elderly drivers (65 years and older) in the Federal Republic of Germany will probably double. Concerns about traffic safety predominate-under the broadly accepted assumption that the elderly drive less cautiously. The most important results of driving tests of elderly drivers (and a comparison group of middle-aged) and their relation to performance measures are presented. The results show that the elderly drivers performed worse in laboratory tests, but in driving tests (in a significant number of different traffic situations) they did not differ unfavourably from the middle-aged drivers.

Tracer kinetic studies of the low density lipoprotein metabolism in the fetal rat: an example for estimation of flux rates in the nonsteady state.

To get insight into the low density lipoprotein (LDL)-apoB flux in the rat fetus near term and in the early postnatal period, homologous apoE-free 125I-labeled LDL was injected into the umbilical vein of the rat fetus immediately after Caesarean section. Since the serum LDL-apoB spontaneously declined after birth, a time-dependent two-pool model was used to calculate the flux rates in the neonate from the specific activities of LDL-apoB up to 15 h post partum. An approximate value of LDL-apoB flux in the fetus at birth was obtained by extrapolation of the kinetic data to the time of injection of the tracer. The data revealed that the turnover of LDL-apoB in the fetus (18.6 micrograms LDL-apoB/h per g body weight) exceeded that in the adult rat (0.4 microgram/h per g body weight) by at least one order of magnitude. Even 15 h after delivery, the LDL-apoB influx amounted to 2.5 micrograms/h per g body weight. The fractional catabolic rate of LDL-apoB in the fetus at term (0.39, h-1) slightly exceeded that in the adult animal (0.15, h-1) and reached the adult level within the first 3 h after birth and remained constant thereafter. In the rat fetus, LDL-apoB flux greatly exceeds that of VLDL-apoB. The data support the view of a direct synthesis and secretion of LDL, most probably by the fetal membranes.

[The sialylation rate of apolipoprotein E in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus]. / Der Sialinisierungsgrad von Apolipoprotein E bei insulinabhängigem (IDDM) und nicht insulinabhängigem (NIDDM) Diabetes mellitus.

The degree of apo E sialylation in VLDL from serum of diabetics and controls was determined by densitometric scanning of the pherograms after isoelectric focusing of the VLDL proteins including treatment with neuraminidase. The distribution pattern of sialylation within the groups of patients and controls followed a Gaussian type. A significantly elevated level of sialylated apo E could be demonstrated in IDDM and NIDDM as compared to the controls. No correlation was found between the apo E phenotype and the diabetic state. From the correlation analysis including the parameters degree of sialylation, age, duration of diabetic state, and blood glucose pattern no significant results were obtained except a significant but only week correlation (r less than 0.3) between sialylation, age, and blood glucose in IDDM patients. Possible consequences of the elevated apo E sialylation in diabetes mellitus are discussed.

Biochemical and ultrastructural studies on the effect of verapamil on formation and secretion of lipoproteins in rat hepatocyte suspensions.

The effect of the calcium channel blocker verapamil on structure, formation and secretion of very-low-density lipoproteins (VLDL) from rat hepatocytes in suspension was examined. After 30 min incubation at a verapamil dose of 200 microM neither free fatty acid (FFA) uptake nor triglyceride (TG) and phospholipid (PL) secretion into the incubation medium were significantly changed. After 90 min incubation the TG secretion was inhibited by about 60%, whereas the PL output was only insignificantly lowered, indicating the secretion of abnormally composed lipoprotein particles. Morphologically, after 30 min incubation the hepatocytes had lost their microvillous border and exhibited a 2-3-fold increase in volume density and average size of the lysosomes. In the Golgi-containing regions an accumulation of smooth-surfaced microvesicles was regularly evident. The configuration of the Golgi complexes was normal. After 90 min incubation the lysosomes showed a further significant elevation in volume and size. The Golgi complexes exhibited only minor changes, but their content in VLDL particles was reduced per microns 2 Golgi complex by about 75%. Commonly, the VLDL were larger and more heterogenous in size. The diameter of those VLDL secreted into the incubation medium ranged from 31 to 84 nm, thus surpassing the control values by 2-3 times. The secretion of large-sized VLDL was regularly associated with the intracytoplasmic appearance of dilated smooth-surfaced vesicles filled with size-modified VLDL. These vesicles were concentrated within Golgi-containing areas from where they were widely dispersed towards the cell periphery.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins as risk indicators of ischemic heart disease.

About 50% of the individuals with a coronary risk show lipid levels within the normal range. Therefore, apolipoprotein profiles could be better risk indicators than TC or TG. Apolipoproteins generally discussed in this context are apo A1, apo B, and apo E. Their diagnostic validity, however, is ambigously evaluated. The individual iso-protein pattern of apo E is important for the differential diagnosis of the type III hyperlipidemia with its strong predisposition for premature atherosclerosis. Moreover, the extent of the apo E sialylation seems to be important because the modification of apo E by sialic acid alters its metabolism. Our date provide evidence that in IDDM and NIDDM the degree of apo E sialylation is increased. Concerning apo A1 and B we tried to find out parameters suitable for the prediction of the coronary risk both in the hyperlipidemic and the normolipidemic state. 64 male survivors of a myocardial infarc"ion and 60 matched controls were included in the study (group I). From group I a supopulation showing non-pathological values for TC and TG was selected (group II with 31 survivors and 44 controls). The diagnostic validity of the parameters apo A1, apo B, TC, HDL-C, apo A1/apo B, TC/apo B, HDL-C/apo B, TG, TG/apo A1, TG/HDL-C, TC-HDL-C/apo B determined by calculation of their sensitivities, specificities, efficiencies, and predictive values. Only the parameters TC/apo B, HDL-C/apo B, and apo B were suitable in the order given for detection of the coronary risk. Using the TC/apo B ratio 71-76% of the controls and 79% of the survivors could be exactly reclassified independent of the group they belonged to.(ABSTRACT TRUNCATED AT 250 WORDS)

Receptor-mediated uptake of homologous low-density lipoproteins by isolated liver parenchymal cells of fetal rats.

The binding and uptake of gold-labeled homologous, apolipoprotein E-free low-density lipoproteins (LDL) by isolated fetal rat liver parenchymal cells in suspension were studied ultrastructurally and morphometrically. Binding experiments using 125I-labeled LDL were also performed. After a 2-h preincubation in a lipoprotein-free medium and a subsequent 1-h postincubation in the presence of LDL-gold, fetal liver parenchymal cells exhibit a binding of 248 +/- 17 gold conjugates/100 micron plasma membrane and an uptake of 235 +/- 17 gold conjugates/100 micron2 cytoplasm. Compared with values obtained from freshly isolated non-preincubated cells, these data correspond to a 15-fold and an 18-fold increase in total binding and uptake of LDL-gold, respectively. Competition experiments reveal that this increase is mainly a result of a 23-fold stimulation of specific binding and a 44-fold stimulation of receptor-mediated uptake of LDL-gold. The 125I-LDL binding experiments give a Kd value of 6.3 X 10(-8) M and a maximum binding capacity of 17.3 fmol LDL/10(6) cells. Our data provide evidence, further to our in vivo studies, that fetal rat liver parenchymal cells possess high-affinity binding sites for native homologous apolipoprotein E-free LDL. These sites may correspond to B, E receptors of adult rat liver parenchymal cells.

Rat LDL metabolism in the perinatal period.

In fetal rats at term LDL carries 75% of the total serum cholesterol, whereas in adult ones this value amounts to 20% only. Using a time-dependent two pool model the flux rates for LDL cholesterol can be calculated for the newborn. The data reveal that at birth the LDL cholesterol flux is 15-20 times higher than in the adult. During the first 2 h of postnatal life the FCR drops down from 0.4 at birth to values measured in the adult. Since at least 75% of LDL is of another origin than VLDL, a direct hepatic LDL synthesis is postulated for the newborn. The liver contributes to about 30% of the total LDL uptake which is mainly realized by a receptor-dependent mechanism, even though the fetus and the newborn exhibit markedly elevated LDL serum concentrations.

Preparation of apoE-free rat low density lipoprotein for catabolic studies.

The use of serum from rat fetuses instead of serum from adult rats for preparation of LDL by preparative ultracentrifugation leads to an LDL fraction containing apoB-100 and apoB-95 as the only protein moieties without need for any further purification. The yield of LDL is five times greater compared to the use of adult rat serum. Lipid composition and particle size of LDL from fetal and adult rats are quite similar. The method described allows a simple way for preparation of sufficient amounts of apoE-free LDL for use in metabolic studies.

Plasma from atherosclerotic patients exerts an increased degradation of platelet-activating factor.

Platelet-activating factor (PAF) is a naturally occurring phospholipid that exerts diverse biological activities. In the present study the degradation of PAF as well as lipid concentrations were measured both in plasma from 28 patients suffering from peripheral vascular disease and 18 healthy volunteers of comparable age. Beside some changes of the lipoprotein pattern it was also found that the capacity to degrade PAF is significantly elevated in the patient group. In view of this finding the question arises whether there is any link between the degradation of PAF and the development of atherosclerosis.

In vivo binding and uptake of low-density lipoprotein-gold- and albumin-gold conjugates by parenchymal and sinusoidal cells of the fetal rat liver.

To elucidate the participation of fetal rat liver cells in the receptor-mediated internalization of low-density lipoproteins (LDL), rat fetuses were injected with either LDL-gold or albumin-gold conjugates. The degree of binding and uptake of LDL-gold and albumin-gold by parenchymal and sinusoidal cells of the fetal rat liver differs markedly. Endothelial cells exhibit low LDL-gold uptake. In contrast, parenchymal cells internalize LDL-gold more actively (45 +/- 8 LDL conjugates/100 micrometers2 cytoplasm within 60 min). Kupffer cells exceed this value by a factor of 20. The uptake of albumin-gold by endothelial and Kupffer cells is high, whereas it is extremely low in parenchymal cells. Estradiol pretreatment causes a significant doubling (p less than 0.05) of the LDL-gold particle density/100 micrometers2 cytoplasm both in parenchymal and Kupffer cells, whereas estradiol has no effect on the albumin uptake. The results strongly indicate that LDL uptake by parenchymal and Kupffer cells in the fetal rat liver is mediated by estrogen-inducible receptors, which may correspond to B, E receptors in the adult liver.

Very-low-density lipoproteins in the fetal rat at term.

VLDL triglyceride influx into fetal serum and the composition of fetal serum VLDL was studied in rats at term. By use of the Triton WR 1339 method the rate of VLDL triglyceride influx into fetal circulation was calculated to be 0.1 mmol/h X 1 serum in comparison to 4.2 mmol/h X 1 in adult rats. Fetal VLDL exhibit a composition differing from that of adults. The experimental data indicate that the main fraction of fetal serum VLDL represents intermediates of VLDL metabolism converted already to apolipoprotein C-free, relatively triglyceride-depleted particles.

Binding and internalization of low density lipoproteins in fetal rat liver at term under in vivo and in vitro conditions.

Binding and internalization of rat low density lipoproteins (LDL) by fetal rat liver cells were studied under in vivo and in vitro conditions by ultrastructural and biochemical methods. By using LDL-gold conjugates it could be shown that on day 22 of gestation hepatocytes and Kupffer cells mainly contribute to specific binding and uptake of LDL, but not endothelial cells. Estrogen administration to the pregnant rats stimulated binding and internalization of LDL-gold. The binding characteristics of isolated fetal hepatocytes were determined by 125I-LDL. The data allow the conclusion that fetal hepatocytes and Kupffer cells possess specific B/E receptors.