[Etiology and significance of growth disturbances of the spine]. / Ätiologie und Bedeutung von Wachstumsstörungen der Wirbelsäule.

BACKGROUND: The majority of growth disturbances of the spine are acquired and their etiology is still unknown. Both scolioses and sagittal profile disorders are most commonly of idiopathic origin. ETIOLOGY: The etiology is multifactorial and besides genetic, hormonal and mechanical factors also metabolic components seem to be involved. The risk of progression of an existing deformity is particularly high during the pubertal growth spurt. Accordingly, regular clinical and radiological controls should be carried out in this vulnerable period. Recently, spinal deformities have been classified according to the time of diagnosis rather than according to their etiology, considering the increasing knowledge about the correlation between spinal and thoracic growth and the associated maturation of the lungs. Therefore, the term "early onset scoliosis" considers all deformities of the spine diagnosed before the age of 10 years. TREATMENT: In the case of failure of conservative treatment options, which have to be applied for as long as possible, definitive spinal fusion surgery should be delayed by the use of growth-sparing surgical techniques, aiming to achieve as normal pulmonary function as possible.

Treatment of early onset spinal deformities with magnetically controlled growing rods: a single centre experience of 30 cases.

PURPOSE: The treatment of early onset scoliosis continues to be a major challenge, even when using motorized growth-sparing implants. We report on 30 cases operated on with magnetically controlled growing rods (MCGRs) at our institution, analyzing radiological parameters and complications, comparing our results with the literature and presenting a special implant fixation technique. A separate focus highlights the challenges of conversion from previous non-motorized implants. METHODS: Consecutive case series. The nature and effects of complications were recorded for all patients. Radiographic evaluations were performed for patients with a minimum follow-up of two years. Separate analyses were carried out for patients who were previously treated with non-motorized growth-sparing implants. RESULTS: There were 12 documented complications in 11/30 (37%) patients leading to 13 unplanned returns to the operating room. In all, 18/30 patients had a minimum follow-up of two years. Major curve and main kyphosis, as well as T1 to T12 and T1 to S1 distances significantly improved with MCGR implantation, however, less in patients converted from previous growth-sparing surgical treatment. While the achieved correction of the major curve was maintained, there was a loss of kyphosis correction with subsequent implant lengthening. Gain in implant length decreased with increasing number of extensions. CONCLUSION: Despite improved patient's comfort, MCGR show a considerable complication rate. Coronal plane deformities can be well controlled, but diminished implant lengthening is already apparent within two years after MCGR implantation. Central databases should help to clarify unresolved aspects and optimize the treatment of these young patients. LEVEL OF EVIDENCE: IV.

Treatment strategy and long-term functional outcome of traumatic elbow dislocation in childhood: a single centre study.

PURPOSE: Traumatic elbow dislocation (TED) is the most common injury of large joints in children. There is an ongoing debate on the optimal treatment for TED. We aimed to assess the functional outcome after operative and nonoperative treatment of TED. METHODS: We analysed the medical records of patients with TED treated at the University Children's Hospital, Basel, between March 2006 and June 2015. Functional outcome was assessed using the Mayo Elbow Performance Score (MEPS) and Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) Sport and Music Module score. These scores were compared between nonoperatively and operatively treated patients. RESULTS: A total of 37 patients (mean age 10.2 years, 5.2 to 15.3) were included. Of these, 21 (56.8%) children had undergone nonoperative treatment, with 16 (43.2%) patients having had operative treatment. After a mean follow-up of 5.6 years (1.2 to 5.9), MEPS and QuickDASH Sport and Music Module scores in the nonoperative group and operative group were similar: MEPS: 97.1 points (SD 4.6) versus 97.2 points (SD 2.6); 95% confidence interval (CI)-2.56 to 2.03); p = 0.53; QuickDASH Sport and Music Module score: 3.9 points (SD 6.1) versus 3.1 points (SD 4.6); 95% CI 2.60 to 4.17; p = 0.94. We noted no significant differences regarding the long-term functional outcome between the subgroup of children treated operatively versus those treated nonoperatively for TED with accompanying fractures of the medial epicondyle and medial condyle. CONCLUSION: Functional outcome after TED was excellent, independent of the treatment strategy. If clear indications for surgery are absent, a nonoperative approach for TED should be considered. LEVEL OF EVIDENCE: Level III - therapeutic, retrospective, comparative study.

[Treatment of early onset scoliosis : How far can we go?]. / Behandlung von frühkindlichen Skoliosen : Wo liegen die Grenzen?

BACKGROUND: Recently, inconsistent definitions of early onset scoliosis (EOS) and a wide variety of treatment options have been observed. OBJECTIVES: To clearly define the term EOS, to depict non-operative and operative treatment options, and to present the limitations of the boundaries of these techniques. METHODS: Review of the literature, including conference presentations and expert opinions, in addition to personal experiences. RESULTS: Early onset scoliosis (EOS) refers to spine deformity that is present before 10 years of age, regardless of etiology. All existing operative treatment options share a high risk of complications. Therefore, non-operative treatment should act as a time-buying approach to postpone surgery. DISCUSSION: Awareness of treatment options and their specific indications, in addition to respecting each patient's individual needs and feasibilities, are crucial for the optimal outcome.

Selective fusion in adolescent idiopathic scoliosis: a radiographic evaluation of risk factors for imbalance.

STUDY DESIGN: Retrospective database, chart and medical imaging review. OBJECTIVES: To report on the outcome and evaluate possible risk factors for postoperative complications following selective spinal fusion in patients with adolescent idiopathic scoliosis (AIS). MATERIALS AND METHODS: All patients with AIS who underwent either a selective thoracic or selective thoracolumbar/lumbar spinal fusion at our institution from January 2001 to December 2011 inclusive were included in this study. The minimum postoperative follow-up period of all patients was 2 years. RESULTS: During the 11-year study period, 157 patients with AIS underwent surgery for their progressive spinal deformity. Thirty patients (19 %) had a selective spinal fusion, with 16 patients (group A) having a selective thoracic, and 14 patients (group B) having a selective thoracolumbar/lumbar spinal arthrodesis. In both groups the main postoperative complications were adding-on (25 % group A, 36 % group B) and coronal decompensation (25 % group A, 29 % group B). In group A, no statistically significant risk factors for postoperative complications were identified. In group B, global coronal balance was identified as a significant risk factor for adding-on. Patients with adding-on had significantly higher coronal balance scores (mean 3.6) than those who did not experience adding-on (mean 1.9) (p = 0.03). In addition, those with adding-on had a significantly smaller bending lumbar Cobb angle (mean 15) than those without adding-on (mean 31.6) (p = 0.015). None of the patients who underwent selective spinal fusion required revision surgery. CONCLUSION: Although the complication rate after performing a selective spinal fusion is high, the revision rate remains low and the debate whether or not to perform a selective spinal fusion will continue.

[Process optimization by central control of acute pain therapy: implementation of standardized treatment concepts and central pain management in hospitals]. / Prozessoptimierung durch zentrale Steuerung der Akutschmerztherapie : Implementierung von standardisierten Behandlungskonzepten und zentralem Schmerzmanagement im Krankenhaus.

BACKGROUND: The aim of this investigation was to describe the effects of standardization and central control of the processes involved in postoperative pain management from patient and employee perspectives. MATERIALS AND METHODS: Patients (n = 282/307) and respective hospital staff (n = 149/119) evaluated the processes, the quality of postoperative pain management and result parameters 3 months before and 12 months after the introduction of standardization of the postoperative pain therapy process using a set of standardized questionnaires. RESULTS: Pain level and the waiting period for an analgesic partially decreased and a higher subjective effectiveness of medication was achieved in patients after the standardization. Patients felt that the pain was taken more seriously and contacted the staff for additional medication more frequently. From an employee viewpoint the quality of care and individual competence and ability to treat pain increased after the introduction of standardization. Pain assessment was improved and employees rated their knowledge and education level as higher than before the intervention. Patients with pre-existing chronic pain and patients with special regional therapy benefited only partially after the introduction and an increase in pain intensity was even observed. CONCLUSIONS: The quality of care was improved by standardization of the postoperative pain management. The legal and practical ability of the nursing stuff to administer pain medication within well-defined margins reduced the dependence on the ward doctor and at the same time patient pain levels. Patients received analgesics more quickly and experienced increased effectiveness. These results should be an incentive to reconsider the importance of the organization of postoperative pain management, because the quality of care with all potential medical and economic advantages, can be easily optimized by such simple mechanisms. They also show that the quality assessment of acute pain and the selection of appropriate indicators need further development.

[Consequences of an accidental aspiration of petroleum in a case of a fire eating man]. / Folgen einer akzidentellen Aspiration von Petroleum bei einem Feuerspucker.

Fire-eater's pneumonitis, caused by aspiration of petroleum, is an infrequent clinical problem in our region. It is an acute inflammatory response of the lungs to the accidental aspiration of hydrocarbons, as shown in our patient. Despite the severe initial clinical und radiological presentation, fire-eater's pneumonitis usually shows a favourable evolution with "restitutio ad integrum". Acute mortality rate is less than 1%. Fire-eater's lung is a medical emergency and needs medical support and surveillance. There is no good evidence that systemic cortico-steroids and antibiotics are effective in the treatment of hydrocarbon aspiration. Concerning chronic lung injury after fire-eater's pneumonitis, there are favorable results from short observational series.

Safe high-pressure freezing of infectious micro-organisms.

We describe how high-pressure freezing of infectious biological material can safely be accomplished with the help of membrane carriers. The method described is easy to perform; however, careful manipulations are required. Existing safety regulations must still be followed. However, the procedure reduces the risk of dissemination of infectious material.

Evaluation of limit feeding varying levels of distillers dried grains with solubles in non-feed-withdrawal molt programs for laying hens.

An experiment was conducted with 672 Hy-Line W-36 Single Comb White Leghorn hens (69 wk of age) to evaluate the effects of feeding varying levels of corn distillers dried grains with solubles (DDGS) with corn, wheat middlings, and soybean hulls on long-term laying hen postmolt performance. The control molt treatment consisted of a 47% corn:47% soybean hulls (C:SH) diet fed ad libitum for 28 d. Hens fed the other 7 treatments were limit fed 65 g/hen per day for 16 d, and then fed 55 g/hen per day for 12 d. Hens on treatments 2 and 3 were fed 49% C:35% wheat middlings (WM) or SH:10% DDGS diets (C:WM:10DDGS, C:SH:10DDGS). Hens on treatments 4 and 5 were fed 49% C:25% WM or SH:20% DDGS diets (C:WM:20DDGS, C:SH:20DDGS). Those on treatments 6 and 7 were fed 47% C:47% DDGS (C:DDGS) or 47% WM:47% DDGS (WM:DDGS) diets. Those on treatment 8 were fed a 94% DDGS diet. At 28 d, all hens were fed a corn-soybean meal layer diet (16% CP) and production performance was measured for 36 wk. None of the hens fed the molt diets went completely out of production, and only the C:SH and C:SH:10DDGS molt diets decreased hen-day egg production to below 5% by wk 4 of the molt period. Postmolt egg production was lowest (P < 0.05) for the C:WM:20DDGS treatment. No differences (P > 0.05) in egg weights were detected among treatments throughout the postmolt period. In addition, no consistent differences were observed among treatments for egg mass throughout the postmolt period. Overall results of this study indicated that limit feeding diets containing DDGS at levels of 65 or 55 g/hen per day during the molt period did not cause hens to totally cease egg production.

Pseudovacuoles--immobilized by high-pressure freezing--are associated with blebbing in walker carcinosarcoma cells.

By applying high pressure freezing and freeze-substitution, we observed large inclusions of homogeneous appearance in the front of locomoting Walker carcinosarcoma cells that have not been described earlier. Live cell imaging revealed that these inclusions were poor in lipids and nucleic acids but had a high lysine (and hence protein) content. Usually one such structure 2-5 mum in size was present at the front of motile Walker cells, predominantly in the immediate vicinity of newly forming blebs. By correlating the lysine-rich areas in fixed and embedded cells with electron microscopic pictures, inclusions could be assigned to confined, faintly stained cytoplasmic areas that lacked a surrounding membrane; they were therefore called pseudovacuoles. After high-pressure freezing and freeze substitution, pseudovacuoles appeared to be filled with 20 nm large electron-transparent patches surrounded by 12 and 15 nm large particles. The heat shock protein Hsp90 was identified by peptide sequencing as a major fluorescent band on SDS-PAGE of lysine-labelled Walker cell extracts. By immunofluorescence, Hsp90 was found to be enriched in pseudovacuoles. Colocalization of the lysine with a potassium-specific dye in living cells revealed that pseudovacuoles act as K+ stores in the vicinity of forming blebs. We propose that pseudovacuoles might support blebbing by locally regulating the intracellular hydrostatic pressure.

Relative sensitivity factors of inorganic cations in frozen-hydrated standards in secondary ion MS analysis.

We describe the measurement, at 100 K, of the SIMS relative sensitivity factors (RSFs) of the main physiological cations Na+, K+, Mg2+, and Ca2+ in frozen-hydrated (F-H) ionic solutions. Freezing was performed by either plunge freezing or high-pressure freezing. We also report the measurement of the RSFs in flax fibers, which are a model for ions in the plant cell wall, and in F-H ionic samples, which are a model for ions in the vacuole. RSFs were determined under bombardment with neutral oxygen (FAB) for both the fibers and the F-H samples. We show that referencing to ice-characteristic secondary ions is of little value in determining RSFs and that referencing to K is preferable. The RSFs of Na relative to K and of Ca relative to Mg in F-H samples are similar to their respective values in fiber samples, whereas the RSFs of both Ca and Mg relative to K are lower in fibers than in F-H samples. Our data show that the physical factors important for the determination of the RSFs are not the same in F-H samples and in homogeneous matrixes. Our data show that it is possible to perform a SIMS relative quantification of the cations in frozen-hydrated samples with an accuracy on the order of 15%. Referencing to K permits the quantification of the ionic ratios, even when the absolute concentration of the referencing ion is unknown. This is essential for physiological studies of F-H biological samples.

Effect of tegaserod on gut transit in male and female subjects.

Tegaserod is a novel selective serotonin receptor type-4 (5-HT(4)) partial agonist that stimulates gastrointestinal (GI) motility. Tegaserod has proven efficacy in irritable bowel syndrome with constipation in women and in men and women with chronic idiopathic constipation. The effects on gastric emptying, small bowel transit and colonic transit have not been studied in detail in male and female subjects. This study aimed therefore to assess the effect of gender on GI transit with and without tegaserod. A randomized, placebo-controlled, double-blind, crossover study was performed in 40 healthy subjects (23 males, 17 females). Each treatment period involved three and a half days of bid treatment with either 6 mg tegaserod or an identical placebo. Transit parameters were assessed by a scintigraphy. Tegaserod significantly accelerated gastric emptying, small bowel and colonic transit times (P<0.05-0.0001). The effect was more apparent in male subjects than in females (P=0.044 to P<0.0001). The most striking prokinetic effects were observed in the upper GI tract (stomach and small intestine). In both healthy male and female subjects, tegaserod markedly accelerated small intestinal transit, and induced a significant increase in gastric emptying time and colonic transit. The results imply that tegaserod is a potent prokinetic agent throughout the GI in both sexes.

Brain connectivity at different time-scales measured with EEG.

We present an overview of different methods for decomposing a multichannel spontaneous electroencephalogram (EEG) into sets of temporal patterns and topographic distributions. All of the methods presented here consider the scalp electric field as the basic analysis entity in space. In time, the resolution of the methods is between milliseconds (time-domain analysis), subseconds (time- and frequency-domain analysis) and seconds (frequency-domain analysis). For any of these methods, we show that large parts of the data can be explained by a small number of topographic distributions. Physically, this implies that the brain regions that generated one of those topographies must have been active with a common phase. If several brain regions are producing EEG signals at the same time and frequency, they have a strong tendency to do this in a synchronized mode. This view is illustrated by several examples (including combined EEG and functional magnetic resonance imaging (fMRI)) and a selective review of the literature. The findings are discussed in terms of short-lasting binding between different brain regions through synchronized oscillations, which could constitute a mechanism to form transient, functional neurocognitive networks.

A rapid microbiopsy system to improve the preservation of biological samples prior to high-pressure freezing.

A microbiopsy system for fast excision and transfer of biological specimens from donor to high-pressure freezer was developed. With a modified, commercially available, Promag 1.2 biopsy gun, tissue samples can be excised with a size small enough (0.6 mm x 1.2 mm x 0.3 mm) to be easily transferred into a newly designed specimen platelet. A self-made transfer unit allows fast transfer of the specimen from the needle into the specimen platelet. The platelet is then fixed in a commercially available specimen holder of a high-pressure freezing machine (EM PACT, Leica Microsystems, Vienna, Austria) and frozen therein. The time required by a well-instructed (but not experienced) person to execute all steps is in the range of half a minute. This period is considered short enough to maintain the excised tissue pieces close to their native state. We show that a range of animal tissues (liver, brain, kidney and muscle) are well preserved. To prove the quality of freezing achieved with the system, we show vitrified ivy leaves high-pressure frozen in the new specimen platelet.

An oscillating cryo-knife reduces cutting-induced deformation of vitreous ultrathin sections.

A new oscillating cryo-knife for producing uncompressed vitreous sections is introduced. The knife is a modified cryo diamond knife that is driven by a piezo translator. Optimal setting for the oscillation was found to be in the inaudible frequency range of 20-25 kHz. Yeast cells and polystyrene spheres were used as model systems to describe compression in the vitreous sections. We found that compression could be reduced by a factor of about 2 when the knife was oscillating. When the oscillator was turned off, sections were compressed by 40-45%. However, only 15-25% compression was obtained when the knife was oscillating. In some cases completely uncompressed sections of yeast cells were produced. It was also found that the amount of compression depends on the specimen itself and on its embedding medium. With the results shown here, we demonstrate that the oscillating knife can produce high-quality vitreous sections with minimum cutting artefacts.

Amorphous solid water produced by cryosectioning of crystalline ice at 113 K.

Amorphous solid (vitreous) water can be obtained by a number of methods, including quick freezing of a very small volume of pure water, low pressure condensation of water vapour on a cold substrate or transformation of hexagonal ice (the ice which is naturally formed) under very high pressure at liquid nitrogen temperature. Larger volumes can be vitrified if cryoprotectant is added or when samples are frozen under high pressure. We show that a sample of 17.5% dextran solution or mouse brain tissue, respectively, frozen under high pressure (200 MPa) into cubic or hexagonal ice can be transformed into vitreous water by the very process of cryosectioning. The vitreous sections obtained by this procedure differ from cryosections obtained from vitreous samples by the irregular aspect of the sections and by small but significant differences in the electron diffraction patterns. For the growing community of cryo-ultramicrotomists it is important to know that vitrification can occur at the knife edge. A vitreous sample is considered to show the best possible structural preservation. The sort of vitrification described here, however, can lead to bad structural preservation and is therefore considered to be a pitfall. Furthermore, we compare these sections with other forms of amorphous solid water and find it similar to high density amorphous water produced at very high pressures (about 1 GPa) from hexagonal ice and annealed close to its transformation temperature at 117 K.

A new approach for cryofixation by high-pressure freezing.

A newly designed high-pressure freezing machine for cryofixation was established and tested (Leica EMPACT), based on ideas originally proposed by Moor & Riehle in 1968. The new machine, essentially an improved version of our prototype, pressurizes the sample to 2000 bar in a small container (using methylcyclohexane as hydraulic fluid) and at the same time cools the outer surface of the container with a jet of liquid nitrogen. The advantage of this approach is that the machine uses little liquid nitrogen and can be built small and light. The machine is able to vitrify and freeze well a variety of specimens, for example, plant leaves, yeast cells, liver or nerve tissue (more samples are shown at: http://www.ana.unibe.ch/empact). Cooling efficiency is the same as in the traditional machines that use liquid nitrogen to pressurize and simultaneously cool the sample.

Minimal compression of ultrathin sections with use of an oscillating diamond knife.

With the aim to minimize compression artefacts in ultrathin sections, coincident with the stroke direction, we have invented an oscillating diamond knife. Results and theoretical considerations explaining its function are discussed. During conventional ultrathin sectioning the resultant compression is in the order of 20-35% of section height. This holds true for sections of samples embedded into Lowicryl HM20 and of the polymer polystyrene, cut with a 45 degrees diamond knife and floated on water. The oscillating knife reduces this compression almost completely. It consists of a diamond knife on which a low voltage piezoelectric translator (piezo) is mounted, which oscillates when the piezo is driven by an alternating voltage source. No additional cutting artefacts were observed in the micrographs when they were compared with sections produced without oscillating the knife.

Matrilin-2, a large, oligomeric matrix protein, is expressed by a great variety of cells and forms fibrillar networks.

Matrilin-2 is a member of the protein superfamily with von Willebrand factor type A-like modules. Mouse matrilin-2 cDNA fragments were expressed in 293-EBNA cells, and the protein was purified, characterized, and used to immunize rabbits. The affinity-purified antiserum detects matrilin-2 in dense and loose connective tissue structures, subepithelial connective tissue of the skin and digestive tract, specialized cartilages, and blood vessel walls. In situ hybridization of 35S-labeled riboprobes localizes the matrilin-2 mRNA to fibroblasts of dermis, tendon, ligaments, perichondrium, and periosteum; connective tissue elements in the heart; smooth muscle cells; and epithelia and loose connective tissue cells of the alimentary canal and respiratory tract. RNA blot hybridization and immunoblotting revealed both matrilin-2 mRNA and protein in cultures of a variety of cell types, confirming the tissue distribution. Alternative splicing affects a module unique for matrilin-2 in all of the above RNA sources. SDS-polyacrylamide gel electrophoresis and electron microscopy reveals matrilin-2 from tissue extracts and cell line cultures as a mixture of mono-, di-, tri-, and tetramers. Matrilin-2 is substituted with N-linked oligosaccharides but not with glycosaminoglycans. Because of other, yet unidentified, cell-type dependent posttranslational modifications, the monomer is heterogeneous in size. Immunofluorescence showed that matrilin-2 functions by forming an extracellular, filamentous network.

Electron beam-induced changes in vitreous sections of biological samples.

Nonpretreated high pressure frozen samples of Zea mays, cartilage and human erythrocytes were cryosectioned and observed at 110K in a cryoelectron microscope. Changes induced by medium doses of electron irradiation (< 10 ke nm-2) are described. After some ke nm-2, the most conspicuous cutting artefacts are erased to a large extent and the visibility of the cell organelles is improved. The sections, compressed in the cutting direction by the sectioning process, shrink once more, in the same direction, when irradiated. This shrinkage depends on the section support and on how the section is adsorbed to it. Shrinkage is not uniform: it is most pronounced in mitochondria, condensed chromatin and nucleolus. This differential shrinkage improves the visibility of major structures on the section and, as a result, 'nicer' images are recorded. However, this apparent improvement is a beam-induced artefact that must be paired with a loss of high resolution information.