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Hintergrund. Unter CRASH-Syndrom wird eine Gruppe von X-chromosomal vererbten Erkrankungen zusammengefasst, die eine Mutation im L1CAM-Gen vorweisen und nach dem Akronym CRASH folgende Symptome vorweisen konnen: Corpus-callosum-Hypoplasie, Retardierung, adduzierte Daumen, spastische Paraplegie und Hydrozephalus. Eine Erkrankung aus dieser Reihe ist der X-chromosomal gebundene Hydrozephalus, erstmals beschrieben von Bickers und Adams 1949 als Hydrozephalus mit Aquaduktstenose (HSAS).

The Ruhr, with an average flow of 80.5 m3/s at its mouth, is a comparatively small tributary to the Rhine River that has to perform an important task: to secure the water supply of more than 5 million people and of the industry in the densely populated region north of the river. The complex water management system and network applied by the Ruhrverband in the natural Ruhr River Basin has been developed step by step, over decades since 1913. And from the beginning, its major goal has been to achieve optimal conditions for the people living in the region. For this purpose, a functional water supply and wastewater disposal infrastructure has been built up. The development of these structures required and still requires multi-dimensional planning and performance. Since the river serves as receiving water and at the same time as a source of drinking water, the above-standard efforts of Ruhrverband for cleaner water also help to conserve nature and wildlife. Ruhrverband has summed up its environmental awareness in the slogan: “For the people and for the environment”. This basic water philosophy, successfully applied to the Ruhr for more than 80 years, will be continued in accordance with the new European Water Framework Directive, enacted in 2000, which demands integrated water resources management in natural river basins, by including the good ecological status of surface waterbodies as an additional goal.

Zusammenfassung: Ethik und Okonomie schliesen sich gegenseitig nicht aus, sondern sind verwandte Begriffe, die Hilfestellung beim Umgang des Menschen mit knappen Ressourcen geben. Die Sicherung der eingesetzten Ressourcen und die Erwirtschaftung von Gewinn sind allgemeine industrielle Zielsetzungen. Produktspezifische Zielsetzungen, wie Optimierung der Arzneimittelsicherheit, die Nutzenstiftung fur Individuum und Gesellschaft, werden diskutiert. Heilung von Krankheit, Steigerung der Lebensqualitat und Verlangerung des Lebens stehen dabei im Vordergrund. Die Beitrage der Pharmaindustrie, ethisch begrundete Forderungen zu erfullen, werden v. a. auf die Ressourcenschonung (z. B. durch Verzicht auf staatliche Forderung) bezogen. Fruhzeitige Kommunikation von Forschungsergebnissen zur intersektoralen Nutzung und freiwilliger Verhaltenkodex, der Informations- und Werbeverhalten der pharmazeutischen Unternehmen regelt, sind weitere ethische Beitrage. In der 3. Welt sieht sich die Pharmaindustrie vor allem der potentiellen Vergeudung wertvoller Medikamente gegenuber, wie sie bei mangelnder Verteilungsinfrastruktur auftritt, wenn gleichzeitig in geeigneteren Gebieten Mangel an Medikamenten auftritt. Der Wert von Arzneimitteln wird durch einen Vergleich von konkurrierenden Therapien (Differenz im Ressourcenverbrauch) definiert. Mogliche Ethikdefizite durch das Fehlen eines direkten Kontaktes des Patienten mit der Industrie und der Quasi-Ponalisierung von Patienten aufgrund von Fehlern im Lebensstil werden andiskutiert. Medical Ethics as Output of Economically Motivated Industrial Objectives Summary: Ethics and economics are not mutually exclusive, but rather related concepts that help the human race in dealing with scarce resources. Safeguarding the resources employed and making a profit are general industrial objectives. Product-specific objectives, such as optimising medicinal safety and creating benefits for the individual and society, are discussed. Healing disease, improving quality of life and prolonging length of life are very important considerations. The contributions of the pharmaceutical industry in fulfilling ethically based demands will be primarily treated as the careful use of resources (e. g. by renunciation of state support). Other ethical contributions are the early communication of research results for intersectoral use and a voluntary code of conduct to regulate the actions of pharmaceutical companies with regard to information and advertising. In the Third World pharmaceutical industry is mainly faced to potential waste of valuable medicines, due to insufficient infrastructure of logistics and distribution capacities in one region, given a shortage of these very medicines in other and better structured regions. The value of medicines is defined by a comparison of competing therapies (difference in consumption of resources). Possible ethical deficiencies arising from a lack of direct contact of the patient with industry and the quasi-penalisation of patients because of faulty lifestyle are briefly discussed.

Der vorliegende Beitrag behandelt neue experimentelle und theoretische Untersuchungen zum Ermudungsverhalten einbetonierter Kopfbolzendubel. Es werden Versuche an Zweifeldtragern unter realitatsnaher Beanspruchung vorgestellt. Dazu wurde eine neuartige Simulation einer Uberfahrt mit Hilfe zweier Hydraulikzylinder realisiert. Es zeigt sich, das das Ermudungsverhalten unter Realbedingungen zum Teil von den Ergebnissen fruherer experimenteller Untersuchungen abweicht. Es werden zusatzlich weggeregelte Push-Out-Versuche vorgestellt, die mit Originalkollektiven der Relativverschiebungen aus den Tragerversuchen belastet wurden und die das Verhalten der Verdubelung im Trager anscheinend gut wiederspiegeln. Die grundsatzlichen Zusammenhange bei der Beschreibung des Ermudungsverhaltens mussen eventuell neu uberdacht werden. Dies wird auf experimentellem Weg und auch anhand von theoretischen Uberlegungen gezeigt.

The installation of about 500 stormwater detention facilities (SDFs) led to a significant drop of the pollution originating from stormwater runoff in the river basin of the Ruhr which covers 4,488 km2. The German technical directives on the design of SDFs are briefly outlined and the specific costs for such plants are given. The average costs for one kilogram COD held back by SDFs in combined systems amount to € 3.73 (calculated without consideration of the subsequent removal in the municipal wastewater treatment plant (WWTP)). The tank volume for stormwater storage can be minimised by application of real-time management systems which allow a dynamic operation of all SDFs in a catchment area.

C1q is the initiator of the classical complement pathway and, as such, is essential for efficient opsonization and clearance of pathogens, altered self-structures, and apoptotic cells. The ceramide transporter protein (CERT) and its longer splicing isoform CERTL are known to interact with extracellular matrix components, such as type IV collagen, and with the innate immune protein serum amyloid P. In this article, we report a novel function of CERT in the innate immune response. Both CERT isoforms, when immobilized, were found to bind the globular head region of C1q and to initiate the classical complement pathway, leading to activation of C4 and C3, as well as generation of the membrane attack complex C5b–9. In addition, C1q was shown to bind to endogenous CERTL on the surface of apoptotic cells. These results demonstrate the role of CERTs in innate immunity, especially in the clearance of apoptotic cells.

Objective: To report late onset cerebral white matter disease as a distinctive phenotype in peroxisome biogenesis disorder (PBD). Background: There is phenotypic and genetic overlap among the PBD known as Zellweger syndrome (ZS), infantile Refsum disease (IRD), and neonatal adrenoleukodystrophy (NALD). Distinctive external features are variable among these three disorders, and neurologic deficit has its onset at birth or in infancy. In a structured follow-up cohort of 25 patients with PBD, not including ZS, three patients had an unusual pattern of cerebral white matter disease with onset past the age of 1, not conforming to any of the classic PBD phenotypes. Methods: Clinical phenotyping and follow-up, peroxisomal biochemical determinations in body fluids and fibroblasts, identification of affected PEX gene by genetic complementation in fibroblasts, and MRI studies. Results: Two unrelated patients with PBD without distinctive external features had normal neurodevelopmental milestones during their first year, followed by rapid deterioration including severe hypotonic pareses, seizures, retinopathy, and deafness. A third patient initially diagnosed with IRD developed cerebral white matter degeneration in the third year of life, complicating the original diagnosis. MRI in all three patients showed cerebral demyelination with sparing of subcortical fibers and pronounced central cerebellar demyelination. Conclusions: Late-onset cerebral white matter disease may occur in PBD, either following IRD or following normal early development and in the absence of distinctive external features. Peroxisome biogenesis disorder should be included in the differential diagnosis of post-infantile onset of cerebral white matter disease.

Comparing international costs in the field of water management is difficult. The frame conditions in the various countries are very different. They influence the costs and particularly the sewage charges in a complex way. Some of these conditions are outlined by analyzing the situation in Germany as a “case study”. An objective comparison should deal with the in situ arising product costs as annual costs. The product costs consist of both the operating and the capital costs. The annual product costs of 34 wastewater treatment plants in six different European countries are presented. The observed differences in the quality of the construction and of the mechanical equipment of the plants were taken into account with different depreciation periods. The product costs in four of six countries, including Germany, were found to be nearly at the same level. Although the German frame conditions are demanding and difficult the expectation of outstanding high product costs was not confirmed.

In the catchment area of the Ruhr, restructuring and upgrading measures in the domain of wastewater and stormwater treatment have been under way since 1990 to successively implement the currently applicable legal requirements for nutrient removal. With 2.1 million inhabitants and a design capacity of 3.7 million population equivalents (PE), it is expected that approximately DM 2 billion still have to be invested from 2000 onward. With this it will be possible to further cut the nutrient load in the Ruhr River, that has been declining consistently since the 1970s: by about 25% for Ntotal and about 10% for Ptotal. The anticipated decrease in ammonia-nitrogen in winter is particularly important for drinking water production from the river water (bank filtration). Whether and to what an extent the expected decline in phosphorus concentrations will curb eutrophication in the Ruhr with its several impounded stretches remains to be seen. Further nutrient load reductions cannot be achieved by sewage treatment-related measures. Load balances underline the adverse impact of diffuse or non-point sources, in particular, for nitrogen. Some potential to further improve the situation is seen in minimizing the nutrient releases from agricultural practices.

Der Beitrag fasst die Ergebnisse juengster experimenteller Untersuchungen zum Ermuedungsverhalten von Kopfbolzenduebeln in Verbundkonstruktionen zusammen. Dabei wird das Nachweisformat des Eurocodes 4, Teil 2 ueberprueft, und noch fehlende Bemessungsgrundlagen werden zur Ergaenzung vorgeschlagen. Es werden Woehlerlinien fuer den Einsatz von Profilblechen vorgestellt, die den Einfluss des Duebeldurchmessers und der Duebeloberlast beruecksichtigen. Ausserdem werden Zeitreihen- und Blockversuche zur Anwendbarkeit der Miner-Regel als Schadensakkumulationshypothese vorgestellt. Die Untersuchungen wurden fuer Kopfbolzen in profilierten Betongurten sowie fuer den Einsatz in Vollbetonplatten durchgefuehrt. (A) Titel in Englisch: The shear connection of steel-concrete composite bridges under non-static load.

This prospective, randomised, double-blind, controlled clinical study was performed at a single tertiary referral centre to test the hypothesis that the prophylactic administration of amrinone before separation of a patient from cardiopulmonary bypass decreases the incidence of failure to wean, and to identify those patients who could be predicted to benefit from such pre-emptive management. Two hundred and thirty-four patients, scheduled to undergo elective cardiac surgery, were randomly allocated to receive either a bolus dose of 1.5 mg.kg−1 amrinone over 15 min, followed by an infusion of 10 µg.kg−1.min−1, or a bolus of placebo of equal volume followed by an infusion of placebo. Treatment with amrinone or placebo was initiated upon release of the aortic cross-clamp, before weaning from cardiopulmonary bypass. Anaesthetic technique, monitoring and myocardial preservation methods were standardised for both groups. Significantly fewer patients failed to wean in the group that received prophylactic amrinone than in the control group (7 vs. 21%, p = 0.002). Amrinone improved weaning success regardless of left ventricular ejection fraction, although this benefit was statistically significant only in the group with left ventricular ejection fractions > 55%. Of the 32 patients who failed to wean from cardiopulmonary bypass, 14 had normal pre-operative left ventricular ejection fractions.

Cost comparison in the field of wastewater treatment is a difficult task, particularly concerning sewages charges in different countries. German wastewater management is, for one thing, known to be very efficient, yet, for another, comparatively costly on an international scale. In this context, the marginal conditions typically prevailing in the field of sewage treatment in Germany should be mentioned: dense population and industrialization with high export-oriented production rates, high-profile purification requirements enforced by law. To establish a valid cost comparison, it is necessary to include both the investment and the operating expenses within the scope of the overall annual costs. The major factors impacting the different cost types are represented. Only if these factors are taken into account and quantified, will cost comparison be fair and lead to useful results. Ten hints for cost minimization are given to serve as a guideline for successful and responsable cost reduction. Cost transparency is the prerequisite for the possibility to develop saving potentials while simultaneously securing the social and political acceptance of the charges levied, and to compare the different plants with one another. Experience from Ruhrverband, a water management association for an entire catchment area, being responsible for planning, building and operation of 94 wastewater treatment plants and other plants for water quantity and water quality management, is reported.

17β-Hydroxysteroid dehydrogenase-3 (17βHSD3) deficiency is an autosomal recessive form of male pseudohermaphroditism caused by mutations in the HSD17B3 gene. In a nationwide study on male pseudohermaphroditism among all pediatric endocrinologists and clinical geneticists in The Netherlands, 18 17βHSD3-deficient index cases were identified, 12 of whom initially had received the tentative diagnosis androgen insensitivity syndrome (AIS). The phenotypes and genotypes of these patients were studied. Endocrine diagnostic methods were evaluated in comparison to mutation analysis of the HSD17B3 gene. RT-PCR studies were performed on testicular ribonucleic acid of patients homozygous for two different splice site mutations. The minimal incidence of 17βHSD3 deficiency in The Netherlands and the corresponding carrier frequency were calculated. Haplotype analysis of the chromosomal region of the HSD17B3 gene in Europeans, North Americans, Latin Americans, Australians, and Arabs was used to establish whether recurrent identical mutations were ancient or had repeatedly occurred de novo. In genotypically identical cases, phenotypic variation for external sexual development was observed. Gonadotropin-stimulated serum testosterone/androstenedione ratios in 17βHSD3-deficient patients were discriminative in all cases and did not overlap with ratios in normal controls or with ratios in AIS patients. In all investigated patients both HSD17B3 alleles were mutated. The intronic mutations 325+ 4;A→T and 655–1;G→A disrupted normal splicing, but a small amount of wild-type messenger ribonucleic acid was still made in patients homozygous for 655–1;G→A. The minimal incidence of 17βHSD3 deficiency in The Netherlands was shown to be 1:147,000, with a heterozygote frequency of 1:135. At least 4 mutations, 325 + 4;A→T, N74T, 655–1;G→A, and R80Q, found worldwide, appeared to be ancient and originating from genetic founders. Their dispersion could be reconstructed through historical analysis. The HSD17B3 gene mutations 326–1;G→C and P282L were de novo mutations. 17βHSD3 deficiency can be reliably diagnosed by endocrine evaluation and mutation analysis. Phenotypic variation can occur between families with the same homozygous mutations. The incidence of 17βHSD3 deficiency is 0.65 times the incidence of AIS, which is thought to be the most frequent known cause of male pseudohermaphroditism without dysgenic gonads. A global inventory of affected cases demonstrated the ancient origin of at least four mutations. The mutational history of this genetic locus offers views into human diversity and disease, provided by national and international collaboration.

Benign familial neonatal convulsions (BFNC) is a rare dominantly inherited epileptic syndrome characterized by frequent brief seizures within the first days of life. The disease is caused by mutations in one of two recently identified voltage-gated potassium channel genes, KCNQ2 or KCNQ3. Here, we describe a four-generation BFNC family carrying a novel mutation within the distal, unconserved C-terminal domain of KCNQ2, a 1-bp deletion, 2513delG, in codon 838 predicting substitution of the last seven and extension by another 56 amino acids. Three family members suffering from febrile but not from neonatal convulsions do not carry the mutation, confirming that febrile convulsions and BFNC are of different pathogenesis. Functional expression of the mutant channel in Xenopus oocytes revealed a reduction of the potassium current to 5% of the wild-type current, but the voltage sensitivity and kinetics were not significantly changed. To find out whether the loss of the last seven amino acids or the C-terminal extension because of 2513delG causes the phenotype, a second, artificial mutation was constructed yielding a stop codon at position 838. This truncation increased the potassium current by twofold compared with the wild type, indicating that the pathological extension produces the phenotype, and suggesting an important role of the distal, unconserved C-terminal domain of this channel. Our results indicate that BFNC is caused by a decreased potassium current impairing repolarization of the neuronal cell membrane, which results in hyperexcitability of the central nervous system.

We report on a boy with congenital pure red blood cell aplasia [Diamond Blackfan anemia (DBA)] and severe congenital hypotonia, macrocephaly, hypertelorism, a broad and tall forehead, medial epicanthus, and facial hypotonia with mouth-breathing and drooling, an affable and out-going personality, and a general psychomotor retardation. These features show similarity to the phenotype of the X-linked FG syndrome. DBA was diagnosed at the age of 4 months, and the boy underwent treatment with transfusion and with prednisolone. He had a normal 46, XY karyotype, but fluorescence in situ hybridization (FISH) analysis to metaphase chromosomes revealed a 3-Mb deletion on 19q13.2. This chromosomal region has previously been linked to the DBA phenotype and one 19q13 microdeletion has been identified in a patient with DBA. This deletion coincides with the deletion reported here. We suggest that the complex phenotype of our patient, including both DBA and the associated features, represent a microdeletion syndrome.

Bei dem 2. Kind konsanguiner turkischer Eltern (unauffallige Familienanamnese, Schwangerschaft, Geburt und Neonatalperiode) wurde in der 6. Lebenswoche eine Arthrogryposis multiplex diagnostiziert. Intensive Krankengymnastik besserte die Kontrakturen nicht. Bis zum Alter von 20 Monaten entwickelten sich die folgenden Symptome: perianale filiforme Tumoren, multiple subkutane Tumoren, schmerzhafte Kontrakturen der Extremitaten, Gingivahyperplasie, periorale Dermatitis, grobe Gesichtszuge, bilaterale Tibiaosteolysen. Die histologische Untersuchung von Gingiva, subkutanen und perianalen Tumoren ergab ein gleichartiges Bild: ein fibroses Gewebe aus kleinen Blutgefasen und Bindegewebszellen in einer homogenen PAS-positiven Matrix. Klinik und Histologie fuhrten zu der Diagnose der juvenilen hyalinen Fibromatose. Diskussion: Bisher wurden ca. 40 Falle dieser autosomal-rezessiv vererbten Erkrankung beschrieben. Die Prognose quoad vitam ist gut, die mentale Entwicklung normal. Die schmerzhaften Kontrakturen und die durch ausgepragte Rezidivneigung und Grosenzunahme gekennzeichneten Tumoren sind nur operativ therapierbar, eine enge interdisziplinare Zusammenarbeit ist erforderlich. Differentialdiagnostisch sind Mukopolysaccharidosen auszuschliesen.

Males with X-linked Kallmann syndrome (XLKS) may have renal agenesis. We studied a large kindred with a history of eight males affected by XLKS born in five generations. Their XLKS was shown to be due to an intragenic mutation of the KAL-1 gene. We also documented three male neonatal deaths due to bilateral renal agenesis (BRA), five males with unilateral renal agenesis (URA), and one female with a pelvic ectopic kidney in this kindred. Of four XLKS males who had renal imaging studies, two had URA. The kindred's KAL-1 mutation was not present in three of the males with URA, the female with the ectopic kidney, nor in preserved autopsy tissue from one infant with BRA. The high frequency of renal agenesis in this family, in the presence and absence of the KAL-1 mutation, suggests an autosomal dominant or X-linked gene which may independently or co-dependently contribute to renal agenesis.

The 22-membered macrocycle, containing four endocyclic pyrazole groups and two exocyclic pyridine groups, viz. (9,22-di(pyridin-2-ylmethyl)-1,4,9,14,17,22,27,28,29,30-decaaza-5,13,18,26-tetramethyl)pentacyclo[24.2.1.1(4,7).1(11,14).1(17,20)]triacontane-5,7(28),11(29),12,18,20(30),24(27),25-octaene (MePy22Pz), has been synthesized in an eleven-step procedure. Two dinuclear copper(II) compounds, viz. [Cu(2)(MePy22Pz)(NO(3))(4)](MeOH)(2) (A) and [Cu(2)(MePy22Pz)(CF(3)SO(3))(2)(H(2)O)(2)](CF(3)SO(3))(2)(MeOH)(2) (B), were prepared with this macrocycle. In both compounds the copper(II) ions are in a square pyramidal N(3)O(2) environment involving a pyrazole nitrogen, a pyridine nitrogen, and a tertiairy amine nitrogen and two oxygen atoms, which stem from two different nitrate anions in compound A and from a triflate anion and a water molecule in compound B. Two of the four pyrazole groups of the macrocycle do not participate in the coordination. The pendent pyridine groups protrude on opposite sides of the macrocycle. Consequently, the copper ions are on different sides of the macrocyclic ring and quite far apart with Cu-Cu distances of 8.668(4) Å in A and 6.814(1) Å in B.

Entwicklungsstorungen konnen erheblich persistieren. Ca. 50–60 % der sprachauffalligen Kinder, die im Vorschulalter diagnostiziert worden sind, weisen auch nach 10 Jahren noch Sprachprobleme auf (39). 80 bis 90 % aller entwicklungsgestorten Kinder haben Probleme beim schulischen Lernen (10, 11). Das Risiko fur Verhaltensauffalligkeiten und Personlichkeitsstorungen (40–60%) ist gegenuber der Normalpopulation signifikant erhoht (3, 30). Relativ gut belegt sind Zusammenhange zwischen Entwicklungsauffalligkeiten und jugendlicher Delinquenz (5, 10). Einer fruhen Diagnostik und Therapie kommt daher eine erhebliche praventive Bedeutung zu. Die Fruherkennung bereitet allerdings erhebliche Probleme. Ein Grosteil der funktionalen Defizite wird erst aufgrund von Leistungsproblemen im Verlauf der Grundschule identifiziert (8, 26). Fur die Diagnostik im Vorschulalter stellen Eltern haufig die einzig zugangliche “Datenquelle” dar.

GH treatment in adults with GH deficiency has numerous beneficial effects, but most studies have been small. We report the results of an Australian multicenter, randomized, double-blind, placebo-controlled trial of the effects of recombinant human GH treatment in adults with GH deficiency. GH deficiency was defined as a peak serum GH of < 5 mU/liter in response to insulin-induced hypoglycemia. Patients were randomly assigned to receive either GH (0.125 U/kg per week for 1 month and 0.25 U/kg per week for 5 months) or placebo. After 6 months, all patients received GH. The primary end points were biochemical responses, body composition, quality of life, and safety. One hundred sixty-six patients (72 females and 91 males) with a mean age of 40 +/- 1 yr (+/- SEM; range 17-67 yr) were recruited. Serum insulin-like growth factor-I (IGF-I) increased from a standard deviation score of -2.64 +/- 0.27 (range -8.8 +3.82; n = 78) to +1.08 +/- 2.87 (range -7.21 to +6.42) at 6 months in the GH/GH group; 38% of the whole group were above the age-specific reference range following treatment [17.6% and 68.9% with subnormal (< 2 SD) or normal (+/- 2 SD) pretreatment levels, respectively]. Fasting total cholesterol (P = 0.042) and low-density lipoprotein cholesterol (P = 0.006) decreased over the first 6 months. Fat-free mass increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or dual energy x-ray absorptiometry (DEXA; P < 0.001). Total-body water increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or deuterium dilution (P = 0.002). Fat mass measured by DEXA (P < 0.001), skinfold thicknesses (P < 0.001), and waist/hip ratio (P = 0.001) decreased in the first 6 months. Most changes in body composition were complete by 3 months of treatment and maintained to 12 months. Whole-body bone mineral density (BMD) (by DEXA) was unaffected by GH treatment. Self-reported quality of life was considered good before treatment, and beneficial treatment effects were observed for energy, pain, and emotional reaction as assessed by the Nottingham Health Profile. In the initial 6 months, adverse effects were reported by 84% of patients in the GH and 75% in the placebo group, with more symptoms relating to fluid retention in the GH group (48% vs. 30%; P = 0.016). Such symptoms were mild and resolved in 70% of patients despite continued treatment. Resting blood pressure did not change over the initial 6 months. In summary, GH treatment in adults with GH deficiency resulted in 1) prominent increases in serum IGF-I at the doses employed, in some cases to supraphysiological levels; 2) modest decreases in total- and low-density lipoprotein cholesterol, together with substantial reductions in total-body and truncal fat mass consistent with an improved cardiovascular risk profile; 3) substantial increases in lean tissue mass; and 4) modest improvements in perceived quality of life. The excessive IGF-I response and side-effect profile suggests that lower doses of GH may be a required for prolonged GH treatment in adults with severe GH deficiency.

Objectives: This study was conducted to compare continuous cardiac output (CCO) with bolus thermodilution cardiac output (BTD) at steady state, and to compare the response time of STAT CCO with that of trend CCO, mean arterial pressure, and mixed venous oxygen saturation (SvO2) during an acute hemodynamic change. Design: Prospective study. Setting: University hospital. Participants: Twenty-nine patients undergoing cardiac surgery or liver transplantation. Interventions: STAT and trend CCO were compared with BTD cardiac output during steady state intraoperatively and postoperatively in the intensive care unit. Ten patients, who required epicardial pacing after cardiac surgery, were studied to compare the response time of STAT CCO with that of trend CCO, mean arterial pressure, and SvO2 after a 10% to 20% increase in pacing rate. Measurements and Main Results: A total of 108 cardiac output data sets were analyzed at steady state. Steady state was defined as stable heart rate and mean arterial pressure (±5%) and stable central venous pressure (±2 mmHg) measured immediately before and after each data set. Cardiac output ranged from 2.3 to 8.5 L/min. The correlation between STAT CCO and BTD was r = 0.94, and for trend CCO and BTD was r = 0.94. The bias and precision for STAT CCO versus BTD were 0.06 L/min (CI 95%: −0.06 to 0.18) and 0.61 L/min. The bias and precision for trend CCO versus BTD were 0.06 L/min (CI 95%: −0.04 to 0.16) and 0.49 L/min. Eleven data sets were analyzed to study response time of STAT CCO, which was defined as the first time the percent change of the mean of each variable was significantly increased from baseline. Significant increases in mean arterial pressure and SvO2 were detected after 30 seconds (2.5%, p = 0.01) and 90 seconds (2.0%, p = 0.04), respectively. A significant increase in STAT CCO was reached at 270 seconds (4.4%, p = 0.006). Trend CCO tended to increase but did not reach statistical significance within 6 minutes. Conclusions: STAT and trend CCO are accurate and precise and show close agreement with BTD cardiac output at steady state. The faster algorithm of STAT CCO offers some advantage over trend CCO during an acute hemodynamic change. However, because of the averaging process for determining CCO, the response time of STAT CCO is slower than that of mean arterial pressure and SvO2.

To investigate the view of parents and professionals on sending children with special educational needs to inclusive schools.54 preschool children in the year before school entry and 155 school children attending a Social Pediatric Center. They displayed motor-, mental-, speech- or sensory handicaps, learning or behavioral disabilities.Questionnaires for parents of preschool- and of school children and questionnaires for the professional caring for the child were evaluated and compared. Parental expectations, experiences concerning school and the severity of disability were determined.135 pupils attended special schools and 20 integrative schools. The parents were generally very content with both types of schools despite the fact that 33% of parents had not have a free choice of the school. They had a positive attitude to inclusive education. Preference for inclusive schooling decreased with increasing severity of the child's disability. The severity of disability was rated similar by parents and by professionals. Parents of preschool children tended more often and parents of school children less often than professionals towards sending the individual child to an inclusive school.Some parents of children with special educational needs would like to send their child to a special school, others prefer inclusive schools. It is paramount to improve the professional advice and guidance to parents since parental options to choose the school for their child are increasing in Germany.Die Studie sollte die Sicht von Eltern und Mitarbeitern eines Sozialpädiatrischen Zentrums zur schulischen Situation von Kindern mit sonderpädagogischem Förderbedarf und zum Besuch integrativer Schulen zeigen.54 Kinder im Jahr vor der Einschulung und 155 Schulkinder. Bei ihnen bestanden körperliche-, geistige-, sprachliche- oder Sinnesbehinderungen, Lern- oder Verhaltensstörungen.Elternfragebögen zu Vorschul- und Schulkindern und ein Mitarbeiterfragebogen zu jedem Kind wurden ausgewertet. Erfragt wurden Schulerfahrungen und -erwartungen der Eltern und die Schwere der Beeinträchtigung. Einschätzungen und Empfehlungen von Eltern und Mitarbeitern wurden verglichen.135 Kinder besuchten eine Sonderschule, 20 eine integrative Schulform. Eltern waren mit der Schule ihrer Kinder sehr zufrieden, obwohl 33% die Schule nicht frei wählen konn­ten. Sie hatten eine positive Einstellung zum gemeinsamen Unterricht von Kindern mit und ohne Beeinträchtigungen. Die Tendenz zu integrativen Schulen sank mit der Schwere der Be­einträchtigung. Eltern und Mitarbeiter schätzten die Schwere der Beeinträchtigung ähnlich ein. Bei Vorschulkindern tendierten die Eltern häufiger, bei Schulkindern seltener als die Mitarbeiter zu einer integrativen Schulform für das jeweilige Kind.Eltern von Kindern mit Lernstörungen oder Behinderungen wünschen für ihre Kinder z.T. eine Sonderschule, z.T eine integrative Schule. Eine verbesserte pädagogische und sozialpädiatrische Beratung bei der Schulwahl ist unabdingbar, vor allem bei gestärktem Elternwahlrecht.

The BZgA study "Youth Sexuality 2010" clarifies the changes that have occurred in the sexual and contraceptive behavior of teenagers and young adults over the last 30 years. Among young Germans, there is now more gender similarity regarding both the age at which intercourse first takes place and contraceptive behavior. The proportion of German teenagers who take no contraceptive precautions when they have intercourse for the first time is now 8%, a lower figure than ever previously recorded. Communication about contraception, both at home and between the partners, is making a substantial contribution to responsible contraceptive behavior on the part of teenagers and young adults. Alongside education about sexuality in the family and at school, there are also structural influences on the positive developments witnessed in Germany. And yet there are still target groups that are inadequately reached. Many migrants are less well informed about bodily processes, their contraceptive practice is not as good, and their religious background tends to exclude them from access to information. Disabled teenagers and young adults constitute a target group about which to date we have insufficient knowledge. Education and social deprivation continue to be important factors in the differences seen in sexual and contraceptive behavior. In this area, proactive efforts are necessary.

A three-stage process starting with the deposition of (In,Ga) 2 Se 3 precursor films has been successful in the fabrication of graded band-gap Cu(In,Ga)Se 2 thin films. In this work we examine (1) the reaction of Cu + Se with (In,Ga) 2 Se 3 , which leads to a spontaneous grading in the Ga content as a function of depth through the film, and (2) modification of the Ga content in the surface region of the film through a final deposition of In + Ga + Se. We show how band-gap grading can be enhanced by the formation of non-uniform precursors, how counterdiffusion limits the degree of grading possible in the surface region, and how the Cu x Se secondary phase acts to homogenize the film composition.

The efficacy and quality of drug formulations are determined mainly by their bioavailability, which is defined by the rate and extent of drug absorption. The zero and first moments of the serum concentration time profile provide relevant information on the bioavailability. On the basis of the body residence time distributions, mean input times may be used as drug absorption rate parameters, but due to computational errors the statistical moments procedure is in some instances of limited value. To circumvent these problems we have developed a procedure to calculate mean input times from input profiles obtained by least-squares decon-volution. We enhanced the performance of the deconvolution method by directly generating initial estimates of one input rate for each sampling interval and compared the statistical properties of various input rate characteristics using data from a bioavailability study on four chlorpro-thixene preparations. The analysis of variance revealed that estimates of mean input times depended on the calculation procedure. Mean input times estimated by the least-squares deconvolution method were more reliable and less variable than those computed as differences of mean body residence times.

Background Despite evidence that regional anesthesia may be associated with fewer perioperative complications than general anesthesia, most studies that have compared cardiac outcome after general or regional anesthesia alone have not shown major differences. This study examines the impact of anesthetic choice on cardiac outcome in patients undergoing peripheral vascular surgery who have a high likelihood of associated coronary artery disease. Methods Four hundred twenty-three patients, between 1988 and 1991, were randomly assigned to receive general (n = 138), epidural (n = 149), or spinal anesthesia (n = 136) for femoral to distal artery bypass surgery. All patients were monitored with radial artery and pulmonary artery catheters. Postoperatively, patients were in a monitored setting for 48-72 h and had daily electrocardiograms for 4-5 days and creatine phosphokinase/isoenzymes every 8 h x 3, then daily for 4 days. Cardiac outcomes recorded were myocardial infarction, angina, and congestive heart failure. Results Baseline clinical characteristics were not different between anesthetic groups. Overall, the patient population included 86% who were diabetic, 69% with hypertension, 36% with a history of a prior myocardial infarction, and 41% with a history of smoking. Cardiovascular morbidity and overall mortality were not significantly different between groups when analyzed by either intention to treat or type of anesthesia received. In the intention to treat analysis, incidences of cardiac event or death for general, spinal, and epidural groups were 16.7%, 21.3%, and 15.4%, respectively. The absolute risk difference observed between general and all regional anesthesia groups for cardiac event or death was -1.6% (95% confidence interval -9.2%, 6.1%) This reflected a nonsignificant trend for lower risk of postoperative events with general anesthesia. Conclusions The choice of anesthesia, when delivered as described, does not significantly influence cardiac morbidity and overall mortality in patients undergoing peripheral vascular surgery.

We report the observation of periodic compositional modulation in ZnSe ${}_{1\ensuremath{-}x}$Te ${}_{x}$ alloys grown by molecular beam epitaxy on vicinal (100) GaAs substrates. The period is highly regular, with typical values between 18 and 32 \AA{}, and is long range in character. X-ray diffraction indicates that the composition varies approximately sinusoidally, resulting in superlattices that are expected to have unique physical properties.

Molecular beam epitaxial growth of the ZnSe1-xTex (x=0.44-0.47) alloy on vicinal (001) GaAs substrates tilted four, six, and nine degree-[111]A or B results in partial phase separation of the alloy with a vertical modulation between different compositions. Transmission electron microscopy images of samples grown on four degree-tilted substrates showed superlattice-like structures, with periods in the range 13.4-28.9Â. Lattice images reveal diffuse interfaces between light and dark bands. Period variations were detected in isolated regions of some samples. We present evidence that the modulation develops at the growth surface, and remains stable in the bulk at temperatures up to 450°C. Satellite spot pairs with approximate indices (h k 1 + δ) were present near the zinc-blende spots in electron diffraction patterns and x-ray diffraction data, as expected from material with a sinusoidal composition profile. The orientation of the spots reveals that the modulation vector is parallel to the growth direction, rather than to [001]. The [111]A- and B-tilted samples showed significant modulation, while the five degree-[110] and on-axis material showed no detectable modulation. The modulation wavelength did not strongly depend on growth temperature in the range examined (285–335°C). Samples showing composition modulation did not exhibit significantly altered low-temperature luminescence spectra from material with no modulation.

The formation chemistry and growth dynamics of thin‐film CuInSe2 grown by physical vapor deposition have been considered along the reaction path leading from the CuxSe:CuInSe2 two‐phase region to single‐phase CuInSe2. The (Cu2Se)β(CuInSe2)1−β (0

Serum amyloid P component (SAP) is a non-fibrillar glycoprotein belonging to the pentraxin family of the innate immune system. SAP is present in plasma, basement membranes, and amyloid deposits. This study demonstrates, for the first time, that the Goodpasture antigen-binding protein (GPBP) binds to human SAP. GPBP is a nonconventional Ser/Thr kinase for basement membrane type IV collagen. Also GPBP is found in plasma and in the extracellular matrix. In the present study, we demonstrate that GPBP specifically binds SAP in its physiological conformations, pentamers and decamers. The START domain in GPBP is important for this interaction. SAP and GPBP form complexes in blood and partly colocalize in amyloid plaques from Alzheimer disease patients. These data suggest the existence of complexes of SAP and GPBP under physiological and pathological conditions. These complexes are important for understanding basement membrane, blood physiology, and plaque formation in Alzheimer disease.

Long‐range order of the CuPt type has been observed in the I‐III‐VI2 material CuInSe2. The ordering was observed by transmission electron diffraction and by high resolution transmission electron microscopy. Comparison with simulated images confirms the CuPt‐type ordering and shows the high degree of ordering. Extrinsic stacking faults were found near domain boundaries of the CuPt‐type ordered material. During irradiation with the electron beam, the transformation from CuPt ordered to the sphalerite or chalcopyrite phase of CuInSe2 was observed.

The band gap and microstructure of Ga0.5In0.5P have been shown to vary with deposition conditions. However, growth on (511)B GaAs substrates has been reported to give Ga0.5In0.5P with band gaps close to that of disordered material. It is shown here, that with appropriate selection of the growth parameters, Ga0.5In0.5P can be grown with low band gap and significant ordering on even the (511)B substrates, implying that surface steps play an important role in the ordering process. For the lattice‐matched composition, a band gap of 1.83 eV was obtained using low growth temperature (575 °C), low growth rate (0.55 μm/h), and high phosphine pressure (5 Torr).

Lissencephaly syndromes are rare disturbances of the neuronal migration with agyria and/or pachygyria. Typical patterns in the EEG of 5 children with lissencephaly are presented. Rhythmic alpha- or beta-waves with high amplitudes of diffuse or fronto-precentral localisation are characteristic in type I lissencephaly. In type II lissencephaly initially theta- or delta-waves of somewhat lower amplitude are observed. Sharp and slow wave-complexes of very high amplitude are found more often in type I lissencephaly. They seem to correlate with the severity of the brain malformation and the epilepsy. In both types of lissencephaly the spatial organisation of the background activity and the sleep-wake differentiation are absent. The EEG of most type I lissencephalies show no reactivity to intravenous benzodiazepines. With increasing age the frequency of the background activity and of the high amplitude rhythmic waves decrease in type I and increase in type II lissencephaly. A complete dedifferentiation of the EEG tracings has been observed in the course of type I lissencephaly. Lissencephaly is diagnosed by imaging techniques. However, with a high probability lissencephaly can be suspected already by its EEG.

The effects of laryngoscopy and tracheal intubation on cerebral and systemic haemodynamics were studied in 30 children. The objective was to identify conditions in which the alterations of cerebral and systemic haemodynamics were minimal. The children were intubated after muscular relaxation and following 10 min of mechanical ventilation with end-tidal halothane concentrations of 1.5%, 2.0% and 2.5%, respectively. With 1.5%, 2.0% and 2.5% end-tidal halothane, the mean flow velocity increased by 26%, 19% and 5%, the mean blood pressure by 14%, 10% and 1%, and the heart rate by 26%, 8% and 5% respectively after intubation. Adverse effects of laryngoscopy and tracheal intubation on cerebral haemodynamics in children can be avoided by adequate anaesthetic protocols.

23 children with acute spinal syndromes are presented. The clinical signs were caused by trauma in 11 patients, by extramedullary tumors in 6, by operations (coarctation of the aorta, scoliosis) in 4 and by encephalomyelitis in 2. Motor signs (flaccid paraplegia or paraparesis, monoplegia, bilateral weakness) and changes of reflex intensities were always observed. Most children presented with disturbances of sensory functions and micturition, some exhibited ataxia. In addition to the neurological signs, plain films of the spine were of diagnostic importance after trauma, for tumors myelography and/or computerized tomography were most useful. The unfavourable prognosis of posttraumatic paraplegia may be improved by early application of corticosteroids in very high doses. The value of GM1-ganglioside is controversial. In cases of external compression by tumors a decompression of the spinal cord is urgent. "Spinal cord monitoring" can be used intraoperatively in surgery of scoliosis and coarctation of the aorta to detect neurological complications early. Differential diagnosis and therapies of encephalomyelitis and Guillain-Barre-Syndrome are discussed.

Delirium is a serious postoperative condition for which few pharmacologic prevention trials have been conducted.The authors tested the efficacy of perioperative olanzapine administration to prevent postoperative delirium in elderly patients after joint-replacement surgery.The authors conducted a randomized, double-blind, placebo-controlled, prophylaxis trial at an orthopedic teaching hospital, enrolling 495 elderly patients age ≥65 years, who were undergoing elective knee- or hip-replacement surgery; 400 patients received either 5 mg of orally-disintegrating olanzapine or placebo just before and after surgery. The primary efficacy outcome was the incidence of (DSM-III-R) delirium.The incidence of delirium was significantly lower in the olanzapine group than in the placebo group; this held true for both knee- and hip-replacement surgery. However, delirium lasted longer and was more severe in the olanzapine group. Advanced age, a high level of medical comorbidity, an abnormal albumin level, and having knee-replacement surgery were independent risk factors for postoperative delirium (Clinicaltrials.gov Identifier: NCT000699946).Administration of 10 mg of oral olanzapine perioperatively, versus placebo, was associated with a significantly lower incidence of delirium. These findings suggest that olanzapine prophylaxis of postoperative delirium may be an effective strategy.

To determine growth, neurological and cognitive development at 5 years of preterm infants with birthweights501 g born in three German tertiary perinatal centres between 1998 and 2001.Structured neurological examination, the Gross Motor Function Classification Scale and the Kaufman-Assessment-Battery Test for Children.Of 107 infants, 48 received immediate life support (gestational age 25.2 weeks [21-30.7]; birth weight 435 g [290-500]) median [range]), 27 (56%) survived until follow-up [95% CI 39-69%], 19 (70%) could be tested. In few infants had catch-up growth taken place. Neurological test results were normal in five infants (26%) and mildly abnormal/severely abnormal in 11 (58%)/3 (16%) infants. Visual impairment was present in eight (42%), and hearing disability in three (16%). The mean mental processing composite (IQ) was 82 [50-104] (median [range]).Of all resuscitated infants with a birthweight501 g, 56% survived to school age. Of these, composite outcome score showed normal development or mild disability in one-half, and moderate or severe disability in the other half of them. Investigators should include such infants in studies and their reports should give specific information about them.