[Pilot study on a modular outpatient treatment programme following public order placements because of endangerment in patients with psychotic disorders]. / Pilot-Anwendung eines modularen ambulanten Therapieprogramms im Anschluss an PsychKG-Unterbringungen wegen Fremdgefährdung bei Patienten mit Psychose-Erkrankungen.

Patients with psychotic disorders who were detained by public order because of endangerment, can be regarded as a population at risk of further endangerment, public order placements and a forensic course. Concepts of specific aftercare for this subgroup are lacking thus far. The present pilot study explores the feasibility of a modular therapeutic outpatient programme that is tailored to specific subgroup needs and is applied over six months. Readmission rates during the intervention period are regarded exploratively.Consecutive screening of all patients placed in general psychiatry by public order during 05 to 11/2012. Included patients received baseline measurements followed by six-month intervention. Individual utilisation of treatment modules and number of readmissions, differentiated according to legal bases were assessed.Inclusion rate: 17.4 % of all screened subjects (115) and 57 % of all potentially includable subjects, dropout rate: 15 %. Mean utilisation rate: 23.5 therapeutic contacts per 6 months. Readmission rate: 50 %, of these 60 % on voluntary legal basis.Study inclusion, mean utilisation and dropout rates attest the feasibility and acceptance of the intervention in the population under study. A preponderance of voluntary vs. compulsory readmissions to hospital during the intervention indicates that in the majority of patients a higher degree of therapeutic cooperativeness can be reached. Further study on reduction of compulsory readmissions and on avoidance of a forensic course by application of the here introduced intervention in combination with methods of risk assessment in a consecutive main project seems justified.

Compartments of the foot: topographic anatomy.

Recent publications have renewed the debate regarding the number of foot compartments. There is also no consensus regarding allocation of individual muscles and communication between compartments. The current study examines the anatomic topography of the foot compartments anew using 32 injections of epoxy-resin and subsequent sheet plastination in 12 cadaveric foot specimens. Six compartments were identified: dorsal, medial, lateral, superficial central, deep forefoot, and deep hindfoot compartments. Communication was evident between the deep hindfoot compartment and the superficial central and deep central forefoot compartments. In the hindfoot, the neurovascular bundles were located in separate tissue sheaths between the central hindfoot compartment and the medial compartment. In the forefoot, the medial and lateral bundles entered the deep central forefoot compartment. The deep central hindfoot compartment housed the quadratus plantae muscle, and after calcaneus fracture could develop an isolated compartment syndrome.

[Orthopaedic Treatment for Patients with Myelomeningocele]. / Orthopädische Behandlung bei Myelomeningozele.

BACKGROUND: Due to prenatal diagnostic and folic acid prophylaxis less children with myelomeningocele are now being born. But they become older and need increasingly more orthopaedic care. The orthopaedic care is aimed at the improvement or the preservation of function. METHOD: In this review the current knowledge from the literature and our approach are presented. This is done in the context of the functional aspects within certain periods of life. Treatment Concept: In the first two years of life, the mobility of MMC children is supported by physiotherapy and orthoses irrespective of the level of the lesion. Afterwards, the optimal orthoses are chosen depending on the muscle power, emerging bone deformities, associated CNS malformation, shunt revisions, obesity and limitations in perception as well as the child's motivation. At school age, it is paramount to encourage independence. Orthotic treatment should be continued as long as the children benefit from it. Orthopaedic operations serve the orthosis fitting and the avoidance of pressure sores. Pathological fractures are common. They should be rapidly recognised in order to avoid further bony deformities. CONCLUSION: The aim of any orthopaedic treatment consists of the avoidance of musculoskeletal deformities in order to support the patient's self employment.

Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing's sarcoma patients.

Natural killer (NK) cell activity has been shown to have potential activity against Ewing's sarcoma (EWS) especially in tumors with low HLA I expression and high NKG2D expression. Two patients with metastatic relapsed and primary metastatic stage IV EWS who had received two courses of high dose chemotherapy with autologous stem cell rescue were transplanted from a haploidentical parental stem cell donor. Patients are alive in ongoing CR for 10.2 and 3.4 years now. Post transplant local second and first relapses were treated successfully in both patients. In vivo IL-2 stimulation not only increased the number and activity of effector cells in one patient but was also associated with severe GvHD. In vitro studies demonstrated high NK cell activity against K562 and relevant activity against EWS cell line A673 post transplant. NK activity was enhanced by cytokine prestimulation as well as by EWS targeting anti-GD2 Ab. Haploidentical hematopoietic stem cell transplantation (HSCT) might contribute to long-term survival by NK cell-mediated effect exerted by donor-derived NK cells. Local tumor recurrence was manageable in both high-risk patients indicating systemic immune control preventing subsequent metastasizing. The efficacy of haploidentical HSCT, cytokine application and tumor targeting antibodies for the use of Ab-dependent cellular cytotoxicity needs evaluation in clinical trials.

Alkali myosin light chains in man are encoded by a multigene family that includes the adult skeletal muscle, the embryonic or atrial, and nonsarcomeric isoforms.

A set of cDNA clones coding for alkali myosin light chains (AMLC) was isolated from fetal human skeletal muscle. Nucleotide sequence analysis and RNA expression patterns of individual clones revealed related sequences corresponding to (i) fast fiber type MLC1 and MLC3; (ii) the embryonic MLC that is also expressed in fetal ventricle and adult atrium (MLCemb); and (iii) a nonsarcomeric MLC isoform that is found in all nonmuscle cell types and smooth muscle. The AMLC gene family in man comprises unique copies for MLC1, MLC3 and MLCemb, and multiple copies for the nonsarcomeric MLC genes. The gene coding for MLC1 and MLC3 is located on human chromosome 2.

A common mutation (epsilon1267delG) in congenital myasthenic patients of Gypsy ethnic origin.

OBJECTIVE: Mutation analysis of the acetylcholine receptor (AChR) epsilon subunit gene in patients with sporadic or autosomal recessive congenital myasthenic syndromes (CMS). BACKGROUND: The nicotinic AChR of skeletal muscle is a neurotransmitter-gated ion channel that mediates synaptic transmission at the vertebrate neuromuscular junction. Mutations in its gene may cause congenital myasthenic syndromes. A recently described mutation in exon 12 of the AChR epsilon subunit (epsilon1267delG) disrupts the cytoplasmic loop and the fourth transmembrane region (M4) of the AChR epsilon subunit. METHODS: Forty-three CMS patients from 35 nonrelated families were clinically classified as sporadic cases of CMS (group III according to European Neuromuscular Centre consensus) and were analyzed for epsilon1267delG by PCR amplification and sequence analysis. RESULTS: The authors report the complete genomic sequence and organization of the gene coding for the epsilon subunit of the human AChR (accession number AF105999). Homozygous epsilon1267delG was identified in 13 CMS patients from 11 independent families. All epsilon1267delG families were of Gypsy or southeastern European origin. Genotype analysis indicated that they derive from a common ancestor (founder) causing CMS in the southeastern European Gypsy population. Phenotype analysis revealed a uniform pattern of clinical features including bilateral ptosis and mild to moderate fatigable weakness of ocular, facial, bulbar, and limb muscles. CONCLUSIONS: The mutation epsilon1267delG might be frequent in European congenital myasthenic syndrome patients of Gypsy ethnic origin. In general, patients (epsilon1267delG) were characterized by the onset of symptoms in early infancy, the presence of ophthalmoparesis, positive response to anticholinesterase treatment, and the benign natural course of the disease.

Occurrence of polychlorinated terphenyls (PCTs) in indoor particulate matter.

In the course of a routine investigation concerned with polychlorinated biphenyl (PCB) contamination of dust collected in classrooms of a junior high school, a group of electron capture detector (ECD)-sensitive compounds with high boiling points were found in addition to PCBs. Using gas chromatographic-mass spectrometric techniques, these compounds were identified as polychlorinated terphenyls (PCTs). Additional measurements indicated that the PCTs were present only in particulate matter collected from the tops of fluorescent light frames but not in air samples obtained concomitantly in the classrooms. Attempts to identify the PCT emission source were unsuccessful. A survey of the literature revealed that PCTs are ubiquitously distributed environmental contaminants, although no data on their indoor occurrence have been reported to date. In view of the toxic effects of PCTs, which seem to be as important as those of PCBs, further attention should be given to the possible presence of PCTs in indoor environments.

The prognostic value of EEG patterns in epilepsies with infantile spasms.

By scoring EEG patterns (hypsarrhythmia = 10, absence of sleeping patterns = 10, focal epileptic discharge = 5, general-treatment or in whom infantile spasms never disappeared even during ACTH. A low voltage EEG did not have any ending ACTH therapy free of seizures showed lower scores compared to those infants relapsing after the end of ACTH treatment or in whom infantile spasms never disappeared even during ACTH. A low voltage EED did not have any prognostic significance. Using EEG scores it might be possible to separate non-responders and responders after 3 weeks of ACTH therapy, thus shortening ACTH treatment in non-responding infants.

[Oral anticoagulation after major hip or knee replacement surgery: a process-driven managerial pharmacoeconomic analysis in German hospitals]. / Orale Antikoagulation bei Hüft- und Kniegelenkersatzpatienten: Prozessanalyse in Akut- und Rehabilitationskliniken.

BACKGROUND: The thrombin inhibitor dabigatranetexilat is used for prophylaxis of venous thromboembolism after total hip or knee replacement surgery (THR/TKR). Patients can take it orally in hospitals. METHOD: In a managerial pharmacoeconomic analysis of six German acute-care hospitals and six German rehabilitation hospitals, the use of dabigatranetexilat was compared with the use of low-molecular-weight heparins. RESULTS: The analysis showed that the new drug led to an economic advantage for an acute-care hospital of 2.43 euro per patient per day. In a rehabilitation hospital, the use of dabigatranetexilat led to an economic advantage of 1.40 euro per patient per day. CONCLUSION: These results have direct implications for drug decisions in hospitals. To demonstrate that fact, the price difference between dabigatranetexilat and low-molecular-weight heparins was derived to lead exactly to their"economic neutrality" from the hospital's point of view.

Self-reported health-related quality of life in children and adolescents with myelomeningocele.

The aim of the study was to investigate self-reported health-related quality of life (HRQOL) in children and adolescents with myelomeningocele (MMC) and to examine the impact of clinical impairments and limitations in activities of daily living (ADL). Fifty patients (28 females, 22 males) between 8 and 16 years of age (mean age 12y 1mo [SD 2y 4mo]) with MMC from three German paediatric centres and their mothers completed standardized measures on HRQOL (KINDL-R) and limitations in ADL (Childhood Health Assessment Questionnaire). Lesion level was thoracic in nine, sacral in 25, and lumbosacral in 11 patients. Twenty-one patients were community walkers, 17 were able to walk in the home, and seven used a wheelchair. Two-thirds had health problems related to the central nervous system causing current difficulties (eight patients had a shunt, six had hydrocephalus, and 10 had a tethered cord). Patients in the study group reported diminished overall HRQOL compared with norm data, specifically in the dimensions of emotional well-being, self-esteem, and peer relations. Adolescents reported diminished HRQOL in the dimension of peer relations. Most medical parameters as well as limitations in ADL were not significantly associated with HRQOL. Our findings confirm the results of studies which dispute a linear inverse association between condition severity and HRQOL and emphasize the importance of peer relations in young patients with MMC.

Identification of the functional promoter regions in the human gene encoding the myosin alkali light chains MLC1 and MLC3 of fast skeletal muscle.

The human gene encoding the alkali myosin light chains (MLC) 1 and 3 of fast skeletal muscle has been isolated. Two separate start sites for transcription have been identified by S1 analysis of muscle RNA. The nucleotide sequences of both proximal promoter regions have been determined and compared to the corresponding gene regions of other species. Several conserved promoter elements were located within 140 nucleotides upstream of the mRNA cap site, whereas further upstream no homologous sequences were found. Unidirectional 5' deletion mutants of both MLC promoters were used to direct bacterial chloramphenicol acetyltransferase activity in transient transfection assays of muscle and nonmuscle cells. Approximately 120 nucleotides of the MLC1 promoter and 80 nucleotides of the MLC3 promoter were sufficient for the transcriptional activation in primary myotubes and to a lower degree also in fibroblasts and hepatocytes. The preferential expression in muscle cells was not dependent on the conserved MLC consensus sequence, CCTTTTATAG, but it absolutely required the CCAT box or the CAT-like box in the MLC1 and MLC3 promoters, respectively. The weak activity of the MLC1 promoter was markedly enhanced in myotubes when DNA from the 3' gene flanking sequence was included in the chloramphenicol acetyltransferase constructs.

[Irreversible valproate-associated liver failure]. / Irreversibles valproatassoziiertes Leberversagen.

A very severely retarded infant with a Dandy-Walker malformation was treated with valproate since the age of 6 months on account of infantile spasms. Three weeks after start of therapy dexamethasone was applied additionally because valproate was ineffective. Seventy-six days after initiation of valproate therapy the infant died with the clinical signs of fulminant valproate-associated hepatotoxicity despite the discontinuation of valproate. In combination with a febrile otitis media the child had been periodically restless and lethargic during the last week prior to liver coma. Activity of liver enzymes remained within normal limits up to two days before coma occurred. Analysis of valproate metabolites by gas chromatography/mass spectrometry yielded unusually high concentrations of the di-unsaturated metabolite E,E-2,3'-dien-valproate before and during liver failure. The concentrations of the main metabolites E-2-en-valproate und 3-keto-valproate remained within the usual range found during valproate therapy at steady state. The oxydation products 4-en-valproate and E-2,4-dien-valproate which are formed by alternative pathways and are considered to be hepatotoxic were detected in very low concentrations only. The application of carnitine, of antioxidants thought to improve the capacity of the free radical scavenger system (selen, vitamin E), and of N-acetylcysteine which can detoxify reactive drug metabolites could not prevent the fatal outcome.

A novel human myosin alkali light chain is developmentally regulated. Expression in fetal cardiac and skeletal muscle and in adult atria.

We have isolated cDNA recombinant phages encoding the embryonic isoform of the myosin alkali light chain (MLC1emb) from a human fetal skeletal muscle library. The cDNA clones were detected by their weak cross-hybridization to a human MLC1F and MLC3F cDNA clone. Nucleotide sequence analysis of the complete cDNA (GT14) revealed an open reading frame for 197 amino acids. The derived protein sequence constitutes the first structural information on this myosin isoform of any organism. Remarkable structural similarities to other alkali MLC polypeptides, particularly to those of the slow-muscle type, are evident. Under conditions of high stringency, the GT14 clone hybridized to an abundant mRNA species in fetal ventricular muscle and adult atrial muscle, whereas in fetal skeletal muscle only a very weakly hybridizing mRNA component was detected. These mRNAs were indistinguishable by size and the thermal stability of their hybrids formed with the DNA insert of clone GT14. We therefore conclude that identical mRNA is expressed in these tissues, presumably transcribed from the same gene. According to its pattern of mRNA expression, the novel MLC isoform described here was designated as "embryonic and atrial myosin light chain" (MLC1emb/A) in reference to its developmental stage-specific and tissue-specific appearance in embryonic skeletal muscle, fetal ventricle and adult atrium.

The repeated sequences (incB) preceding the protein E gene of plasmid mini-F are essential for replication.

At the XhoI site (45.08F) of plasmid mini-F a deletion of 649 bp was generated employing exonuclease Bal31. By this deletion nucleotide sequences functioning as origin II and the four 19 bp direct repeats constituting the incB region in front of the E protein gene were removed from the plasmid. Analysis of proteins radioactively labelled in Escherichia coli mini-cells indicated that all mini-F encoded proteins are expressed. However, the plasmid carrying the deletion was not capable of replicating from the primary origin (origin I, 42.6F). Recently a smaller deletion at the XhoI site (45.08F) of about 300 bp, removing only the region functioning as origin II and replicating from origin I, was described by Tanimoto and Iino (1984, 1985). The data presented suggest that the incB repeats are essential for the initiation of replication from origin I, and possibly also from origin II, and seem not to be engaged in the autoregulation of E protein expression.

Effect of halothane on metabolic ATP and induced aggregation of human blood platelets.

The general anaesthetic halothane decreases both the metabolic ATP level and the aggregability of blood platelets. Evaluation of the dose dependence of these halothane effects reveals that the loss of aggregability is not the direct result of an impaired energy metabolism.

The alkali light chains of human smooth and nonmuscle myosins are encoded by a single gene. Tissue-specific expression by alternative splicing pathways.

Human smooth muscle and nonmuscle cells express closely related myosin alkali light chains which are different from the isoforms present in striated muscle tissues. To date no information on the amino acid sequence of these mammalian nonstriated muscle isoforms has been available. We have isolated full-length cDNA clones encoding the nonmuscle (lym4) and smooth muscle (GT6) myosin light chains (MLCs) from cultured human lymphoblasts and heart aorta smooth muscle cells, respectively. Here we present the complete nucleotide sequences for both cDNA clones, together with the deduced amino acid sequences for the peptides. Both cDNAs contain the same open reading frame for 151 amino acids with 5 amino acid differences located in the C terminus. These differences are encoded by a block of 44 nucleotides which is present only in the smooth muscle (SM) mRNA. To identify the human gene coding for the two MLC isoforms, we have isolated and sequenced the nonmuscle (NM)/SM MLC gene, together with several intronless pseudogenes. A single functional gene was found containing 7 exons which are utilized for the coding information of the SM MLC mRNA. In contrast, the NM MLC mRNA does not contain sequences encoded by exon 6 which corresponds to the 44 nucleotides expressed in SM mRNA. This genomic configuration suggests that both the smooth muscle and nonmuscle MLCs in man are generated from the identical primary transcript by alternative splicing pathways taking place in a tissue-dependent manner.

Psychological disorders in crippled children. A comparative study of children with and without brain damage.

A detailed standardised study was made of all crippled children aged between five and 15 years and of normal intelligence on the local-authority lists of handicapped children in three London boroughs. Psychiatric disorder was twice as common in children whose crippling was due to cerebral disease or damage rather than some peripheral lesion. As the groups were well matched in terms of physical incapacity and social background, it was concluded that brain damage was responsible for the children's increased vulnerability to emotional problems. Brain damage was also associated with a marked increase in reading difficulties and a lowering of intelligence within the normal range. Psychiatric disorder was found to be related not only to cerebral injury but also to various types of family disturbance. It is concluded that emotional and behavioural disturbance stemmed from both an increased biological vulnerability and psychosocial hazards.