Traumatic lumbar disc herniation: A systemic case review and meta-analysis.

Introduction: Traumatic lumbar disc herniation (TLDH) without fracture in the in-situ motion segment is a rare occurrence compared with degenerative herniation. Research question: This study provides a systematic discussion of various aspects related to the diagnosis of TLDH. Material and methods: This review includes 12 cases of TLDH with MR-images since 2009 published in the PubMed and one adjunct illustration. The cases were categorized into two groups for a comprehensive analysis, TLDH with or without in-situ segment fracture. Additionally, we reported a case of a 43-year-old female patient with a recent stenosing TLDH at L5/S1, accompanied by a large sequestration (disc herniation stage-4, and Michigan State University Classification: MSU 3-AB) and an endplate compression fracture at L2 (AO A1). Results: Isolated traumatic lumbar disc herniation is possible, but it is required exclude cases with fractures in the in-situ motion segment. Discussion and conclusion: Trauma with related injury mechanisms is the highest priority for the diagnosis of TLDH. Low-grade disc degeneration without significant instability could be accepted for diagnosing TLDH. A TLDH on MR images might show a slightly lower T2-signal compared to the CSF and a homogeneous T1-signal like the spinal cord, as well as a similar STIR-signal of the sequestration and CSF. If necessary, a histological examination could be performed to evaluate the degenerative changes in the injured disc, especially to assist the evaluation due to legal reasons.

Gender associated developmental trajectories of SDQ-dysregulation profile and its predictors in children.

BACKGROUND: Severe mood dysregulation is common in childhood and can be highly impairing. The Dysregulation Profile (DP) can be considered as a broader phenotype of emotional dysregulation, including affect, cognition and behaviour. Since mood dysregulation may persist, but differently in boys and girls, the gender associated course needs to be considered longitudinally to gain a better insight in order to support the children more adequately. This study is focusing on gender associated subgroup trajectories of the Strengths and Difficulties Questionnaire-Dysregulation Profile (SDQ-DP) in middle childhood (9-13 years of age) and includes the potential impact of clinical and psychosocial characteristics. METHOD: The data set was available from the BELLA study on mental health and well-being in children and adolescents, which is the mental health module of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). A representative epidemiological sample of 564 children living in Germany was examined at three assessment points over 2 years (data collection 2003-2006). The SDQ-DP of children aged 9-13 years was evaluated using Latent Class Growth Analysis (LCGA). RESULTS: For both genders three trajectories with low (girls 67.0% and boys 59.5%), moderate (girls 28.0% and boys 31.7%) and high SDQ-DP (girls 5.0% and boys 8.8%) scores were detected. The courses of low and moderate subgroups were stable, while in the high SDQ-DP subgroup boys showed a decreasing and girls an increasing trend in symptom severity on a descriptive level. The results of the multinomial logistic regression analyses revealed a significant influence of mainly externalising but also internalising problems both increasing the risk of moderate and high SDQ-DP in both genders. Good quality of life was a protective factor for the SDQ-DP course in all subgroups. CONCLUSION: In addition to the known clinical and scientific value of the SDQ-DP, three distinguishable trajectories of SDQ-DP in boys and girls could be found. High externalising problems at the beginning of the trajectory were associated with an undesirable course of SDQ-DP. These findings might be helpful for better psychoeducation, counselling and monitoring in clinical cases and public health.

Indications for total hip arthroplasty in young adults - idiopathic osteoarthritis seems to be overestimated.

PURPOSE: New aspects like acetabular overcoverage, acetabular retroversion and proximal femoral head-neck dysplasia have been detected as a main cause of osteoarthritis. The study addresses the detection of reasons for osteoarthritis requiring THA in young adults. We wanted to prove the hypothesis that idiopathic reasons play an overestimated role in osteoarthritis in young patients. MATERIALS AND METHODS: 228 total hip arthroplasties in patients aged ≤ 60 years were performed at our institution. After the detection of the primary reasons for osteoarthritis of the hip, the radiographic pictures of all other patients were analyzed for radiographic signs of hip dysplasia or femoroacetabular impingement. For interobserver quality testing, this was done by two different observers. RESULTS: 132 patients were initially classified as having idiopathic osteoarthritis of the hip.  There was no pathological radiographic finding in only 5 patients. 80 patients presented a reduced head-neck offset as a sign of CAM impingement with a mean head ratio of 1.52 ±â€Š0.35 and an alpha angle of 62.8 ±â€Š9.28°. 21 patients presented a figure-8 sign as an indicator for acetabular retroversion. 68 patients presented at least one radiographic finding for "dysplasia" and 60 patients at least one radiographic finding for excessive "overcoverage". The Bland-Altman Plot for testing interobserver reliability demonstrated good interobserver agreement. CONCLUSION: Idiopathic OA in young adults is rare if you look hard enough for the underlying pathology. If treated, patients might benefit and THA could be postponed for several years.

Clear-cell sarcoma of the soft tissue--a rare diagnosis with a fatal outcome.

Clear-cell sarcomas account for less than 1% of all soft tissue tumours. They most often occur in middle-aged adults as a deeply located lesion with predilection to the tendons and aponeuroses. The aim of the present study was to show possible influencing factors on the outcome after surgical treatment in a detailed case series. We reviewed the medical records of 11 patients with the diagnosis of a clear-cell sarcoma of the soft tissue. These cases were analysed with regard to age, gender, localisation, tumour size, recurrence free survival and overall survival. A minimum follow up of 12 months was achieved. The mean age at the point of diagnosis was 47.9 years. Metastases occurred after a mean of 19.2 months. In the cases with a tumour diameter >5 cm, metastases occurred earlier. When treated in a specialist centre, metastases occurred later. Patients died a mean of 18.4 months after developing metastatic disease. Patients with tumour size >5 cm at the point of primary diagnosis died earlier than patients with a tumour size <5 cm. It is important to detect clear-cell sarcomas as soon as possible and the final surgical treatment should be performed in a centre familiar with the treatment of soft tissue tumours not only to prolong overall survival, but also to treat the patient in a multiprofessional team.

Myositis proliferans: diagnosis and therapy of a pseudosarcomatous soft tissue lesion.

Myositis proliferans is a soft tissue neoplasia with rare incidence. In the most cases, it is localized in the region of the neck, shoulder, pelvis and thigh. Due to its rapid growth and histological picture, the tumour may appear as a malignant neoplasia. We report the case of a 29-year-old woman suffering from an increasing painful swelling of the left proximal lower leg. Performed biopsies and histological examinations provided the diagnosis of myositis proliferans adjacent to the fibula, which responded to local resection and did not recur after 2 years. We show the importance of adequate diagnostic and therapeutic approach to avoid unnecessary and probably radical overtherapy of the patient.

[Problem cases of metatarsalgia]. / Problemfälle bei Metatarsalgie.

Metatarsalgia is characterized by pain under the metatarsal heads and is a very common cause of foot pain among adults. Symptoms can be isolated or in combination with accompanying deformities occurring in the forefoot and/or hindfoot. In the foreground of the treatment is the exhaustion of conservative forms of therapy to minimize the symptoms of local pressure increase and callus under the metatarsal heads. In addition, various surgical methods are available, such as corrective osteotomy of the metatarsal bone, soft tissue interventions and the correction of associated deformities. The indications for surgical intervention should be made with caution in order to avoid failures and complaints persisting after surgery. The most common problems are an inadequate indication for surgery, technical problems and insufficient postoperative treatment.

[Posterior and transforaminal lumbar interbody fusion (PLIF/TLIF) for the treatment of localised segment degeneration of lumbar spine]. / Posteriore und transforaminale lumbale interkorporelle Fusion (PLIF/TLIF) zur Therapie des lokalisierten Segmentaufbrauchs der LWS.

BACKGROUND: Chronic intractable low back pain is one of the most common orthopaedic diagnoses, with an enormous socioeconomic impact. The surgical treatment by posterior transpedicular instrumentation and interbody fusion of the affected segments is an established procedure after exhaustion of conservative therapies. Due to different study data on the clinical and functional results after posterior (PLIF) and transforaminal (TLIF) interbody fusion, our own patient population was analysed retrospectively. PATIENTS AND METHODS: Included were 143 patients who had been treated surgically at our institution between 1999 and 2006 by one of the two methods (PLIF, n = 68; TLIF, n = 75). In addition to general demographic data, results of three questionnaires (Oswestry disability index, numeric rating scale, Roland Morris score) were retrospectively analysed before surgery and in the general follow-up - identifying clinical and functional results of patient satisfaction. RESULTS: All patients had been suffering in spite of the exhaustion of conservative therapies for at least six months of chronic low back pain prior to surgery. The mean age at surgery was 52 years. The complication rate was 23 %, the revision rate 15 %. Overall, there was a high patient satisfaction in follow-up. In ODI, a significant decrease in pain-related disability was observed from 49.8 % preoperatively to 24.7 % after surgery (p < 0.0001). This functional improvement was present in all aetiological subgroups irrespective of the fusion length. A statistically significantly better functional outcome was achieved in the ODI in the PLIF group (improvement 27.2 % vs. 23.1 %, p < 0.0001). The preoperative baseline regarding pain was assessed in the NRS on average at 6.5 points. Postoperatively, it decreased to 3.34 points (p < 0.0001). The functional limitation due to existing back pain was assessed preoperatively with an average of 13.08 points. Postoperatively a significant reduction to 6.19 points was observed (p < 0.0001). Group- or operation-specific differences were not statistically significant. CONCLUSION: The data of this study indicate that both TLIF and PLIF techniques are possible surgical treatment methods for patients with resistant chronic low back pain. With both techniques a clear benefit regarding quality of life and function for the operated patients is achievable, if the correct surgical indication is given.

Multiple hybrid polyketide synthase/non-ribosomal peptide synthetase gene clusters in the myxobacterium Stigmatella aurantiaca.

Many bacterial and fungal secondary metabolites are produced by polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). Recently, it has been discovered that these modular enzymatic systems can also closely cooperate to form natural products. The analysis of the corresponding biosynthetic machineries, in the form of hybrid systems, is of special interest for combinatorial biosynthesis, because the combination of PKS and NRPS can lead to an immense variety of structures that might be produced. During our screening for hybrid PKS/NRPS systems from myxobacteria, we scanned the genome of Stigmatella aurantiaca DW4/3-1 for the presence of gene loci that encode both the PKS and NRPS genes. In addition to the previously characterized myxothiazol system, we identified three further hybrid loci, three additional PKS and one further NRPS gene locus. These were analyzed by hybridization, physical mapping, PCR with degenerate oligonucleotides and sequencing of fragments of the gene clusters. The function of these genes was not known but it had already been speculated that one compound produced by the strain and detected via HPLC was a secondary metabolite. This was based on the observation that its production is dependent on an active copy of the phosphopantetheinyl transferase gene mtaA. We show here that one of the identified hybrid gene loci is responsible for the formation of this secondary metabolite. In agreement with the genetic data, the chemical structure resembles a cyclic polypeptide with a PKS sidechain. Our data show that S. aurantiaca has a broader genetic capacity to produce natural products than the number of compounds isolated from the strain so far suggests.

Evolution of a 6-200 Mb long-range repeat cluster in the genus Mus.

By fluorescence in situ hybridization, we mapped the location of genes associated with the Sp100-rs cluster, a long-range repeat cluster in chromosome 1 of the house mouse, Mus musculus. The cluster comprises between 60 and 2000 repeats and extends over 6-200 Mb of the M. musculus genome, depending on the source of the cluster. The cluster evolved during the last two million years in the genus Mus in the lineage to which M. musculus belongs. The Asiatic mouse species M. caroli is not in this lineage and does not possess the cluster. M. caroli represents the ancestral genomic organization of the cluster source components Sp100, Csprs and Ifi75: they are located close to each other in the same chromosome band (1D). However, Sp100-rs, the principal gene of the cluster, is not present in the M. caroli genome. It is a chimeric M. musculus gene that arose by fusion of Csprs and the 5' part of Sp100. Sp100-rs and Ifi75 are homogeneously distributed throughout the cluster while Sp100 and Csprs in its original sequence context flank the cluster on opposite sides. Our results suggest a model for the origin and evolution of the long-range repeat cluster by duplication, gene fusion and amplification.

In vitro reconstitution of the myxochelin biosynthetic machinery of Stigmatella aurantiaca Sg a15: Biochemical characterization of a reductive release mechanism from nonribosomal peptide synthetases.

Microorganisms produce iron-chelating compounds to sequester the iron essential for growth from the environment. Many of these compounds are biosynthesized by nonribosomal peptide synthetases, some in cooperation with polyketide synthases. Myxochelins are produced by the myxobacterium Stigmatella aurantiaca Sg a15, and the corresponding gene cluster was cloned recently. We have undertaken to express heterologously the myxochelin biosynthetic machinery in Escherichia coli. To activate the involved proteins posttranslationally, they were coexpressed with the phosphopantetheinyltransferase MtaA from the myxothiazol biosynthetic gene cluster. Phosphopantetheinylation of the carrier proteins could be verified by protein mass analysis. Six active domains in proteins MxcE, MxcF, and MxcG are capable of assembling myxochelin from ATP, NAD(P)H, lysine, and 2,3-dihydroxybenzoic acid in vitro. This fact demonstrates that the condensation domain of MxcG performs two condensation reactions, creating the aryl-capped alpha-amide and the aryl-capped gamma-amide of the molecule. A previously unknown type of reductive release is performed by the reduction domain of MxcG, which alternatively uses NADPH and NADH to set free the peptidyl-carrier protein-bound thioester as an aldehyde and further reduces it to the alcohol structure that can be found in myxochelin A. This type of reductive release seems to be a general mechanism in polyketide and nonribosomal peptide biosynthesis, because several systems with C-terminal similarity to the reductase domain of MxcG can be found in the databases. Alternatively, the aldehyde can be transaminated, giving rise to a terminal amine.

Source and component genes of a 6-200 Mb gene cluster in the house mouse.

We identified and analyzed the genes Sp100, Csprs, and Ifi75 in two members of the genus Mus, M. musculus and M. caroli. Sp100 is a nuclear dot gene; Csprs and Ifi75 are novel genes encoding a putative G-protein coupled receptor (GPCR) and a putative transcriptional coactivator, respectively. A fourth gene, Sp100-rs, occurs in M. musculus, but not in M. caroli. Sp100-rs is a chimeric gene which arose by fusion of Sp100 and Csprs copies. Sp100-rs and Ifi75 are components of a repeat cluster that extends over 6-200 Mb of the M. musculus genome. The Sp100-rs fusion gene arose only 1-2 million years ago and has become fixed and amplified in M. musculus. Although the gene is transcribed, it appears to have no function. The repeat cluster may have become fixed in the species as a 'hitchhiker' in a 'selective sweep'.

Novel features in a combined polyketide synthase/non-ribosomal peptide synthetase: the myxalamid biosynthetic gene cluster of the myxobacterium Stigmatella aurantiaca Sga15.

BACKGROUND: Myxobacteria have been well established as a potent source for natural products with biological activity. They produce a considerable variety of compounds which represent typical polyketide structures with incorporated amino acids (e.g. the epothilons, the myxothiazols and the myxalamids). Several of these secondary metabolites are effective inhibitors of the electron transport via the respiratory chain and have been widely used. Molecular cloning and characterization of the genes governing the biosynthesis of these structures is of considerable interest, because such information adds to the limited knowledge as to how polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) interact and how they might be manipulated in order to form novel antibiotics. RESULTS: A DNA region of approximately 50000 base pairs from Stigmatella aurantiaca Sga15 was sequenced and shown by gene disruption to be involved in myxalamid biosynthesis. Sequence analysis reveals that the myxalamids are formed by a combined PKS/NRPS system. The terminal NRPS MxaA extends the assembled polyketide chain of the myxalamids with alanine. MxaA contains an N-terminal domain with homology to NAD binding proteins, which is responsible during the biogenesis for a novel type of reductive chain release giving rise to the 2-amino-propanol moiety of the myxalamids. The last module of the PKS reveals an unprecedented genetic organization; it is encoded on two genes (mxaB1 and mxaB2), subdividing the domains of one module from each other. A sequence comparison of myxobacterial acyl-transferase domains with known systems from streptomycetes and bacilli reveals that consensus sequences proposed to be specific for methylmalonyl-CoA and malonyl-CoA are not always reliable. CONCLUSIONS: The complete biosynthetic gene cluster of the myxalamid-type electron transport inhibitor from S. aurantiaca Sga15 has been cloned and analyzed. It represents one of the few examples of combined PKS/NRPS systems, the analysis and manipulation of which has the potential to generate novel hybrid structures via combinatorial biosynthesis (e.g. via module-swapping techniques). Additionally, a new type of reductive release from PKS/NRPS systems is described.

The myxochelin iron transport regulon of the myxobacterium Stigmatella aurantiaca Sg a15.

The biosynthetic gene cluster of the myxochelin-type iron chelator was cloned from Stigmatella aurantiaca Sg a15 and characterized. This catecholate siderophore was only known from two other myxobacteria. The biosynthetic genes of 2,3-dihydroxybenzoic acid are located in the cluster (mxcC-mxcF). Two molecules of 2, 3-dihydroxybenzoic acid are activated and condensed with lysine in a unique way by a protein homologous to nonribosomal peptide synthetases (MxcG). Inactivation of mxcG, which encodes an adenylation domain for lysine, results in a myxochelin negative mutant unable to grow under iron-limiting conditions. Growth could be restored by adding Fe3+, myxochelin A or B to the medium. Inactivation of mxcD leads to the same phenotype. A new type of reductive release from nonribosomal peptide synthetases of the 2, 3-dihydroxybenzoic acid bis-amide of lysine from MxcG, catalyzed by a protein domain with homology to NAD(P) binding sites, is discussed. The product of a gene, encoding a protein similar to glutamate-1-semialdehyde 2,1-aminomutases (mxcL), is assumed to transaminate the aldehyde that is proposed as an intermediate. Further genes encoding proteins homologous to typical iron utilization and iron uptake polypeptides are reported.

Stigmatella aurantiaca Sg a15 carries genes encoding type I and type II 3-deoxy-D-arabino-heptulosonate-7-phosphate synthases: involvement of a type II synthase in aurachin biosynthesis.

3-Deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthases catalyse the first step of the shikimate pathway. Two unrelated DAHP synthase types have been described in plants and bacteria. Two type II (aroA(A2) and aroA(A5)) and one type I DAHP synthase gene (aroA001) were identified from the myxobacterium Stigmatella aurantiaca Sg a15. Inactivation of aroA(A5) leads to a mutant that is impaired in the biosynthesis of aurachins, which are electron transport inhibitors and contain an anthranilate moiety. Feeding of anthranilic acid to the mutant culture restores production of aurachins. Inactivation of aroA(A2) and aroA001 does not impair production of aurachins or other known secondary metabolites of S. aurantiaca Sg a15.

Silencing of the Y-chromosomal gene tspy during murine evolution.

We have studied the process of tspy gene silencing in murine evolution. We have isolated functional tspy sequences from Apodemus agrarius, A. sylvaticus, A. flavicollis, and Mus platythrix (subgenus Pyromys) and nonfunctional tspy sequences from species of the subgenus Mus. We present two alternative models as to how tspy may have lost its function in the murine lineage.

Transcription and proper splicing of a mammalian gene in yeast.

The house mouse strain C57BL/6 harbours 64 copies of the multicopy gene Sp100-rs. Three of these are contained in the yeast artificial chromosome (YAC) clone yMm75. Four Sp100-rs transcripts of 3.0, 2.6, 1.6 and 1.3kb were detected by Northern hybridization in the yMm75-harbouring line of Saccharomyces cerevisiae. Additional and less abundant transcripts were detected by RT-PCR. With one exception, the YAC-derived Sp100-rs transcripts were a subset of those found in the C57BL/6 mouse. This indicates transcription and proper splicing of murine pre-mRNAs in yeast. Analysis of the splice sites shows that the yeast splicing machinery accepts splice sites that deviate from the standard yeast consensus sequences. It may be feasible, therefore, at least in a fair proportion of cases, to exploit the mammalian mRNAs present in transgenic yeast for gene recognition of YAC-inserts.

New lessons for combinatorial biosynthesis from myxobacteria. The myxothiazol biosynthetic gene cluster of Stigmatella aurantiaca DW4/3-1.

The biosynthetic mta gene cluster responsible for myxothiazol formation from the fruiting body forming myxobacterium Stigmatella aurantiaca DW4/3-1 was sequenced and analyzed. Myxothiazol, an inhibitor of the electron transport via the bc(1)-complex of the respiratory chain, is biosynthesized by a unique combination of several polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS), which are activated by the 4'-phosphopantetheinyl transferase MtaA. Genomic replacement of a fragment of mtaB and insertion of a kanamycin resistance gene into mtaA both impaired myxothiazol synthesis. Genes mtaC and mtaD encode the enzymes for bis-thiazol(ine) formation and chain extension on one pure NRPS (MtaC) and on a unique combination of PKS and NRPS (MtaD). The genes mtaE and mtaF encode PKSs including peptide fragments with homology to methyltransferases. These methyltransferase modules are assumed to be necessary for the formation of the proposed methoxy- and beta-methoxy-acrylate intermediates of myxothiazol biosynthesis. The last gene of the cluster, mtaG, again resembles a NRPS and provides insight into the mechanism of the formation of the terminal amide of myxothiazol. The carbon backbone of an amino acid added to the myxothiazol-acid is assumed to be removed via an unprecedented module with homology to monooxygenases within MtaG.

Melithiazols, new beta-methoxyacrylate inhibitors of the respiratory chain isolated from myxobacteria. Production, isolation, physico-chemical and biological properties.

New antibiotic compounds, melithiazols, were isolated from the culture broth of strains of the myxobacteria Melittangium lichenicola, Archangium gephyra, and Myxococcus stipitatus. The compounds belong to the group of beta-methoxyacrylate (MOA) inhibitors and are related to the myxothiazols. The melithiazols show high antifungal activity, but are less toxic than myxothiazol A and its methyl ester in a growth inhibition assay with mouse cell cultures. The melithiazols inhibit NADH oxidation by submitochondrial particles from beef heart. Melithiazol A blocks the electron transport within the bc1-segment (complex III) and causes a red shift in the reduced spectrum of cytochrome b.

Metabolic diversity in myxobacteria: identification of the myxalamid and the stigmatellin biosynthetic gene cluster of Stigmatella aurantiaca Sg a15 and a combined polyketide-(poly)peptide gene cluster from the epothilone producing strain Sorangium cellulosum So ce90.

Myxobacterial strains producing polyketides (PKs) assumed to be biosynthesized by a type I polyketide synthase (PKS) were analysed. Myxobacteria also produce a variety of polypeptides (PP) and PKs with incorporated amino acids ('mixed PK-PP'). In order to be able to identify the biosynthetic gene clusters for these metabolites a PCR based approach has been developed to clone ketosynthase (KS) domains of PKS genes from these organisms. Conserved regions of peptide synthetases of the non-ribosomal type (NRPS) were also amplified via PCR. KS fragments from Stigmatella aurantiaca Sg a15 were used for chromosomal gene inactivation experiments resulting in a series of mutants including such that were unable to produce stigmatellins and myxalamids. A NRPS fragment and PKS fragments from Sorangium cellulosum So ce90 were used to identify cosmids hybridizing with both types of probes from a genomic library. Both a NRPS and a PKS fragment were cloned and sequenced from a relatively short restriction fragment of one of these cosmids. The method described here should be very useful to clone and identify PKS, NRPS and mixed PKS-NRPS from myxobacteria in general and thereby open opportunities to use the biochemical diversity of these bacteria for genetic engineering and combinatorial biosynthesis.

Pericentric satellite DNA and molecular phylogeny in Acomys (Rodentia).

Satellite DNAs (stDNAs) of four Acomys species (spiny-mice), A. cahirinus, A. cineraceus, A. dimidiatus and A. russatus, belong to closely related sequence families. Monomer sizes range from 338 to 364 bp. Between-species sequence identity was from 81.0% to 97.2%. The molecular phylogeny of the sequences helps to clarify the taxonomy of this 'difficult' group. The A. dimidiatus genome contains about 60000 repeats. According to the restriction patterns, repeats are arranged in tandem. The stDNA maps to the centromeric heterochromatin of most autosomes, both acrocentric and metacentric, but appears to be absent in the centromeric region of Y chromosomes. A well-conserved centromere protein B (CENP-B) box is present in the stDNA of A. russatus while it is degenerated in the other species.