Reaction of Pertechnetate in Highly Alkaline Solution: Synthesis and Characterization of the Nitridotrioxotechnetate Ba[TcO3 N].

The preparation of novel technetium oxides, their characterization and the general investigation of technetium chemistry are of significant importance, since fundamental research has so far mainly focused on the group homologues. Whereas the structure chemistry of technetium in strongly oxidizing media is dominated by the Tc O 4 - ${{\left[{\rm { Tc}}{{\rm { O}}}_{{\rm { 4}}}\right]}^{-}}$ anion, our recent investigation yielded the new Tc O 3 N 2 - ${{\left[{\rm { Tc}}{{\rm { O}}}_{{\rm { 3}}}{\rm { N}}\right]}^{{\rm { 2}}-}}$ anion. Brown single crystals of Ba[TcO3 N] were obtained under hydrothermal conditions starting from Ba(OH)2 ⋅ 8H2 O and NH4 [TcO4 ] at 200 °C. Ba [ Tc O 3 N ] ${{\rm { Ba[Tc}}{{\rm { O}}}_{{\rm { 3}}}{\rm { N]}}}$ crystallizes in the monoclinic crystal system with the space group P21 /n (a=7.2159(4) Å, b=7.8536(5) Å, c=7.4931(4) Šand ß=104.279(2)°). The crystal structure of Ba [ Tc O 3 N ] ${{\rm { Ba[Tc}}{{\rm { O}}}_{{\rm { 3}}}{\rm { N]}}}$ consists of isolated Tc O 3 N 2 - ${{\left[{\rm { Tc}}{{\rm { O}}}_{{\rm { 3}}}{\rm { N}}\right]}^{{\rm { 2}}-}}$ tetrahedra, which are surrounded by Ba2+ cations. XANES measurements complement the oxidation state +VII for technetium and Raman spectroscopic experiments on Ba[TcO3 N] single crystals exhibit characteristic Tc-O and Tc-N vibrational modes.

TDM-controlled ring resonator arrays for fast, fixed-wavelength optical biosensing.

A novel control concept for serial ring resonator arrays based on a time-division multiplex (TDM) approach is presented. It allows fast sampling rates in terms of biological kinetics. The novelty consists of using both thermal tuning of the effective refractive index and thermo-optical multiplexing for the silicon-on-insulator (SOI) ring resonator arrays, without the need for a tunable laser source. Using a fixed wavelength, fast read-out rates of 100 Hz are demonstrated for each ring.

Gait analysis in tumor patients after distal femoral resection and implantation of a megaprosthesis.

We analysed nine patients who had had a megaprosthesis implanted into the distal femur and knee joint for treatment of sarcomas. Data obtained from the leg operated on were compared with those from the contralateral side and healthy volunteers. Gait data, kinematics, ground reaction forces and the EMG from five muscles around the knee joint were analysed by means of a video-based analysis system recording data from reflection markers ; a Kistler-plate recorded the GRF and a ten channel surface EMG the muscle activity. Muscle around the knee showed a cocontraction between the extensor and flexor muscles in the thigh and the calf in the operated leg as well as contralaterally. Gait characteristics exhibited a reduced speed, -cadence, and a shorter step. This correlated with a reduced flexion in the hip and knee joint. The GRF exhibited significant changes in the data representing the reduced gait dynamic.

[Post-treatment rehabilitation after autologous chondrocyte implantation: State of the art and recommendations of the Clinical Tissue Regeneration Study Group of the German Society for Accident Surgery and the German Society for Orthopedics and Orthopedic Surgery]. / Nachbehandlung bei der autologen Chondrozytentransplantation: Eine Bestandsaufnahme und Empfehlung der AG Klinische Geweberegeneration der DGU/DGOOC.

BACKGROUND: Over the course of the past two decades autologous chondrocyte implantation (ACI) has become an important surgical technique for treating large cartilage defects. The original method using a periostal flap has been improved by using cell-seeded scaffolds for implantation, the matrix-based autologous chondrocyte implantation (mb-ACI) procedure. MATERIAL AND METHODS: Uniform nationwide guidelines for post-ACI rehabilitation do not exist. A survey was conducted among the members of the clinical tissue regeneration study group concerning the current rehabilitation protocols and the members of the study group published recommendations for postoperative rehabilitation and treatment after ACI based on the results of this survey. RESULTS: There was agreement on fundamentals concerning a location-specific rehabilitation protocol (femoral condyle vs. patellofemoral joint). With regard to weight bearing and range of motion a variety of different protocols exist. Similar to this total agreement on the role of magnetic resonance imaging (MRI) for postsurgical care was found but again a great variety of different protocols exist. CONCLUSIONS: This manuscript summarizes the recommendations of the members of the German clinical tissue regeneration study group on postsurgical rehabilitation and MRI assessment after ACI (level IVb/EBM).

Design rules for p-i-n diode carriers sweeping in nano-rib waveguides on SOI.

In this paper we present a detailed analysis of the carrier lifetime for a p-i-n junction on silicon nano-rib waveguides. Several factors determining efficiency of carriers removal from the waveguiding region will be discussed. We compare different structure geometries and spacings between p and n doped regions to show the way to optimize electrons and holes sweeping for CW nonlinear optical devices.

Hydrogel matrix presence and composition influence drug responses of encapsulated glioblastoma spheroids.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with median patient survival of 12-15 months. To facilitate treatment development, bioengineered GBM models that adequately recapitulate the in vivo tumor microenvironment are needed. Matrix-encapsulated multicellular spheroids represent such model because they recapitulate solid tumor characteristics, such as dimensionality, cell-cell, and cell-matrix interactions. Yet, there is no consensus as to which matrix properties are key to improving the predictive capacity of spheroid-based drug screening platforms. We used a hydrogel-encapsulated GBM spheroid model, where matrix properties were independently altered to investigate their effect on GBM spheroid characteristics and drug responsiveness. We focused on hydrogel degradability, tuned via enzymatically degradable crosslinkers, and hydrogel adhesiveness, tuned via integrin ligands. We observed increased cellular infiltration of GBM spheroids and increased resistance to temozolomide in degradable, adhesive hydrogels compared to spheroids in non-degradable, non-adhesive hydrogels or to free-floating spheroids. Further, a higher infiltration index was noted for spheroids in adhesive compared to non-adhesive degradable hydrogels. For spheroids in degradable hydrogels, we determined that infiltrating cells were more susceptible to temozolomide compared to cells in the spheroid core. The temozolomide susceptibility of the infiltrating cells was independent of integrin adhesion. We could not attribute differential drug responses to differential cellular proliferation or to limited drug penetration into the hydrogel matrix. Our results suggest that cell-matrix interactions guide GBM spheroid drug responsiveness and that further elucidation of these interactions could enable the engineering of more predictive drug screening platforms. STATEMENT OF SIGNIFICANCE: Glioblastoma multiforme (GBM) multicellular spheroids hold promise for drug screening and development as they better mimic in vivo cellular responses to therapeutics compared to monolayer cultures. Traditional spheroid models lack an external extracellular matrix (ECM) and fail to mimic the mechanical, physical, and biochemical cues seen in the GBM microenvironment. While embedding spheroids in hydrogel matrices has been shown to better recapitulate the tumor microenvironment, there is still limited understanding as to the key matrix properties that govern spheroid responsiveness to drugs. Here we decoupled and independently altered matrix properties such as degradability, via an enzymatically degradable peptide crosslinker, and cell adhesion, via an adhesive ligand, giving further insight into what matrix properties contribute to GBM chemoresistance.

[Methods of health economic evaluation for health services research]. / Methoden der gesundheitsökonomischen Evaluation in der Versorgungsforschung.

On August 30, 2010, the German Network for Health Services Research [Deutsches Netzwerk Versorgungsforschung e. V. (DNVF e. V.)] approved the Memorandum III "Methods for Health Services Research", supported by the member societies mentioned as authors and published in this Journal [Gesundheitswesen 2010; 72: 739-748]. The present paper focuses on methodological issues of economic evaluation of health care technologies. It complements the Memorandum III "Methods for Health Services Research", part 2. First, general methodological principles of the economic evaluations of health care technologies are outlined. In order to adequately reflect costs and outcomes of health care interventions in the routine health care, data from different sources are required (e. g., comparative efficacy or effectiveness studies, registers, administrative data, etc.). Therefore, various data sources, which might be used for economic evaluations, are presented, and their strengths and limitations are stated. Finally, the need for methodological advancement with regard to data collection and analysis and issues pertaining to communication and dissemination of results of health economic evaluations are discussed.

Sequence-dependent cross-resistance of combined radiotherapy plus BRAFV600E inhibition in melanoma.

INTRODUCTION: Treatment of patients with metastatic melanoma is hampered by drug-resistance and often requires combination with radiotherapy as last-resort option. However, also after radiotherapy, clinical relapses are common. METHODS & RESULTS: Our preclinical models indicated a higher rate of tumour relapse when melanoma cells were first treated with BRAFV600E inhibition (BRAFi) followed by radiotherapy as compared to the reverse sequence. Accordingly, retrospective follow-up data from 65 stage-IV melanoma patients with irradiated melanoma brain metastases confirmed a shortened duration of local response of mitogen-activated protein kinase (MAPK)-inhibitor-pretreated compared with MAPK-inhibitor-naïve intracranial metastases. On the molecular level, we identified JARID1B/KDM5B as a cellular marker for cross-resistance between BRAFi and radiotherapy. JARID1Bhigh cells appeared more frequently under upfront BRAFi as compared with upfront radiation. JARID1B favours cell survival by transcriptional regulation of genes controlling cell cycle, DNA repair and cell death. CONCLUSION: The level of cross-resistance between combined MAPK inhibition and radiotherapy is dependent on the treatment sequence. JARID1B may represent a novel therapy-overarching resistance marker.

Cementless fixation of megaprostheses using a conical fluted stem in the treatment of bone tumours.

We reviewed 25 patients in whom a MUTARS megaprosthesis with a conical fluted stem had been implanted. There were three types of stem: a standard stem was used in 17 cases (three in the proximal femur, nine in the distal femur and five proximal tibia), a custom-made proximal femoral stem in four cases and a custom-made distal femoral stem in four cases. The mean age of the patients was 40.1 years (17 to 70) and the mean follow-up was for 2.5 years (0.9 to 7.4). At follow-up two patients had died from their disease: one was alive with disease and 22 were disease-free. One of 23 prostheses had been removed for infection and another revised to a cemented stem. The mean Musculoskeletal Tumor Society score was 24.9 (12 to 30) and the mean Karnofsky index was 82% (60% to 100%). There was no radiological evidence of loosening or subsidence. Stem stress shielding was seen in 11 patients and was marked in five of these. There were five complications, rupture of the extensor mechanism of the knee after extra-articular resection in two patients, deep venous thrombosis in one, septic loosening in one, and dislocation of the hip in one. The survival rate after seven years was 87% (95% confidence interval (CI) 83 to 91) for the patients and 95% (95% CI 91 to 99) for the megaprosthesis. A longer follow-up is needed to confirm these encouraging results.

Clathrin-mediated endocytosis of MUC1 is modulated by its glycosylation state.

MUC1 is a mucin-like type 1 transmembrane protein associated with the apical surface of epithelial cells. In human tumors of epithelial origin MUC1 is overexpressed in an underglycosylated form with truncated O-glycans and accumulates in intracellular compartments. To understand the basis for this altered subcellular localization, we compared the synthesis and trafficking of various glycosylated forms of MUC1 in normal (Chinese hamster ovary) cells and glycosylation-defective (ldlD) cells that lack the epimerase to make UDP-Gal/GalNAc from UDP-Glc/GlcNAc. Although the MUC1 synthesized in ldlD cells was rapidly degraded, addition of GalNAc alone to the culture media resulted in stabilization and near normal surface expression of MUC1 with truncated but sialylated O-glycans. Interestingly, the initial rate of endocytosis of this underglycosylated MUC1 was stimulated by twofold compared with fully glycosylated MUC1. However, the half-lives of the two forms were not different, indicating that trafficking to lysosomes was not affected. Both the normal and stimulated internalization of MUC1 could be blocked by hypertonic media, a hallmark of clathrin-mediated endocytosis. MUC1 endocytosis was also blocked by expression of a dominant-negative mutant of dynamin-1 (K44A), and MUC1 was observed in both clathrin-coated pits and vesicles by immunoelectron microscopy of ultrathin cryosections. Our data suggest that the subcellular redistribution of MUC1 in tumor cells could be a direct result of altered endocytic trafficking induced by its aberrant glycosylation; potential models are discussed. These results also implicate a new role for O-glycans on mucin-like membrane proteins entering the endocytic pathway through clathrin-coated pits.

[Osteochondritis Dissecans of the Talus - A Critical Review]. / Osteochondrosis dissecans tali ­ eine kritische Übersicht.

The etiology remains unclear. Mechanical factors seem to play an important role. Most histologies report clefts between the cartilage and bone and necrotic areas. Several classifications have been published based on observations from imaging techniques or on intraoperative findings. Clinical symptoms are unspecific. Imaging techniques are of great importance: X-rays of the ankle joint enable a quick diagnostic overview. MRT is the imaging-technique of choice for diagnosing OCDT-lesions. Regarding treatment, a tremendous number of retrospective publications exist. Only a few are classified as level I or II papers. Patients with open physes and low-grade lesions have good results with conservative therapy. Adults do not profit from a longer conservative procedure. Where surgery is necessary, the procedure depends on the stage of the lesion and on the state of the cartilage. With intact cartilage, retrograde procedures or transchondral drilling are to be favoured. Where the cartilage is damaged, several techniques can be used: while techniques such as drilling and microfracturing, or matrix-associated microfracturing produces repair cartilage, other techniques reconstruct the defect with osteochondral grafts or cell-based procedures such as chondrocyte transplantation. Regarding the outcome, it is difficult to make a precise, scientifically-based recommendation which has been confirmed by more than one prospective study. Only limited recommendations are possible: In juveniles with intact cartilage, initially conservative treatment is indicated. If there is no improvement, conservative invasive techniques such as drilling may help. In adults conservative therapy should be limited to a few weeks. Regarding the surgical treatment options, there is a tendency towards better results with procedures which reconstruct the bone and the cartilage and there is also a trend towards better long-term results when co-morbidities are treated. Severe grades of osteoarthrosis are rare.

Dedifferentiated chondrosarcoma--a fatal disease.

BACKGROUND: We report on 13 patients with dedifferentiated chondrosarcomas. The mean age of the patients at diagnosis was 59.8 years. Nine patients were classified as stage IIB and four as stage III. METHODS: In 11/13 cases surgery was performed. Mostly, limb salvage with tumour resection and implantation of a megaprosthesis was done; three patients needed amputation or disarticulation. In one out of three patients with a pelvic tumour resection was followed by implantation of a pelvic replacement; the other two patients received tumour resection with autologous stabilisation of the pelvis. Surgical margins were wide in six patients, marginal in two and intralesional in three. Adjuvant chemotherapy was given to five patients. RESULTS: Recurrence was detected in 5/11 of the patients operated on: in two with wide, in one with marginal, and in two with intralesional resection. No recurrence was seen in 5/11 patients: in four after wide and in one after marginal resection. In one patient the stage was unknown. At follow-up 11 patients were dead of disease (DOD), one dead of unknown reason (DOU) and one alive with disease (AWD). The mean survival time was 9.7 months. Metastasis to different anatomical sites was evident after a period of 10 months. CONCLUSIONS: Our results resemble those reported in the literature. DDCS is rare and is the primary malignant bone tumour with the worst prognosis. Surgery is the most important procedure, although it is unclear whether a radical resection improves the long-term results. Information regarding neoadjuvant and/or adjuvant therapy with chemotherapy is very limited.

Muscular involvement in Behçet's disease: case report and review of the literature.

Acute necrotizing myositis is described in a 22-yr-old man with clinically diagnosed Behçet's disease. Light microscopic examination revealed a prominently granulocytic-monocytic infiltration of the muscle with severe necrosis. An infectious (bacterial, fungal or parasitic) etiology could be excluded by specific staining techniques and by immunohistochemistry. Vascular deposition of immune complexes was detected by direct immunofluorescence. Electron microscopy revealed severe structural damage and phagocytosis of muscle fibers. In the endomysium, leukocytes and occasional erythrocytes were found. Virus-like particles were not seen. The relevant literature on muscular involvement in Behçet's disease is reviewed. It is suggested that two different stages of inflammation occur in Behçet's disease. In the acute stage it presents as a granulocytic-monocytic necrotizing reaction developing from a neutrophil-mediated vasculitis. In the later phase lymphocytic infiltrations predominate. Despite the rare involvement of muscles the diagnosis of Behçet's disease should be considered particularly in younger patients presenting with muscular symptoms like pain and swelling pre-dominantly of the lower extremities.

The in vitro influence of different culture conditions on the potential of sheep rib perichondrium to form hyaline-like cartilage. Evaluation of gluing materials used for in vivo graft fixation.

The effectiveness of autologous rib perichondrium for repair of full-thickness hyaline cartilage defects has been shown experimentally and clinically in various reports. The purpose of this study was to examine the behaviour of sheep rib perichondrial tissue under in vitro conditions and the influence of different culture matrices in order to evaluate possible stimulating effects. Rib perichondrium was obtained from sheep used for an experimental in vivo trial. After removal of adjacent cartilage remnants the tissue was divided and specimens cultured for 14 days in different ways. Explants cultured on collagen sponges (group A), fibrin glue (group B) and cellulose acetate filter (group C) were examined histologically, histochemically, histomorphometrically and autoradiographically. Clear differentiation of perichondrial cells towards a chondrocyte-like cell shape, particularly in the proliferation zone, was noticed on all matrices. These cells synthesized new matrix substances comparable to the ground substance normally present in hyaline cartilage. Morphometric comparison of tissue differentiation on different culture matrices revealed no significant differences in proliferation rates.

Characterization of osteoblast-like cells from fetal rat calvaria.

An improved method is described for the isolation of osteoblast-like cells from fetal rat calvaria. The cells are mononuclear, 8.3 mu in diameter, alkaline phosphate positive, and possess rough endoplasmic reticulum, mitochondria, Golgi, and cytoplasmic processes. Isolated bone cells synthesize collagen and cholesterol, grow to confluence in primary culture, and respond to hormonal stimulation.

Motoneurons of M. semitendinosus in domestic and wild pigs. A horseradish peroxidase and cord-survey study.

In domestic and wild pigs motor nuclei of the M. semitendinosus were labelled by retrograde transport of horseradish peroxidase (HRP) from muscle to spinal cord. Further motoneurons in the lumbosacral cord were stained with Luxol-fast-blue and cresyl violet. Motoneurons innervating M. semitendinosus were present in the ventral horns of the last (6th) lumbal and the first sacral cord segments. They were localized within two motor columns lying parallel to each other in the medial and lateroventral position. Both parts of the semitendinosus motor nuclei showed a spindle-like shape with both cranial and caudal enlargements. Localization, extent, and shape of the semitendinosus motor nuclei were similar in domestic and wild pigs. The average motoneuron diameter was larger in domestic than in wild pigs. The lumbosacral cord of the wild pig was thicker than that of the domestic pig. It is suggested that the size of alpha-motoneurons has increased as a result of selective breeding after domestication. This process might correlate with a higher incidence of myopathies in domestic pigs.

[Legg-Calvé-Perthes disease. The value of MRT in its early diagnosis and the assessment of its course]. / M. Legg-Calvé-Perthes. Wertigkeit der MRT in der Frühdiagnostik und Verlaufsbeurteilung.

We report on the value of MRT in diagnosis and follow-up of Perthes' disease. 38 children who were clinically suspect of suffering from Perthes' disease were examined by conventional x-ray and MRT. 25 children were proven to have Perthes' disease, 12 of them in an early stage. During the onset of the disease MRT showed a higher sensitivity (58% vs 50%) and accuracy (74% vs 71%) than conventional x-ray while specificity was equal (83% for both). Additionally, MRT in combination with the still obligatory x-ray gave no false-positive results. In some cases, the diagnosis may be found up to 6 weeks earlier using MRT. Conservative therapeutic regimens obviously will not profit from this. Although excluding other diseases is certainly helpful, the value of MRT as a primary diagnostic procedure is limited. During follow-up, MRT helps to reduce the number of x-ray examinations since it can easily assess the containment of the hip and the bone marrow revitalisation. Scintigraphy, another valuable method to judge revitalisation, should remain limited to selected cases, as it requires significant amounts of radiation.

Autologous perichondral tissue for meniscal replacement.

Our aim was to examine the potential of autologous perichondral tissue to form a meniscal replacement. In 18 mature sheep we performed a complete medial meniscectomy. The animals were then divided into two groups: 12 had a meniscal replacement using strips of autologous perichondral tissue explanted from the lower rib (group G) and six (group C) served as a control group without a meniscal replacement. In all animals restriction from weight-bearing was achieved by means of transection and partial resection of tendo Achillis. Six animals (four from group G and two from group C) were each killed at 3, 6 and 12 months. The grafts and the underlying articular cartilage were removed and studied by gross macroscopic examination, light microscopy, SEM, polarised light examination, and by biomechanical tests. In all the transplanted animals a new perichondral meniscus developed. After three months the transplants resembled normal menisci in size and thickness, while in the control animals only small rims of spontaneously grown tissue were seen. Microscopically, the perichondral menisci showed a normal orientation of collagen fibres and normal cellular characteristics, but in the central region, areas of calcification disturbed the regular tissue differentiation. Healing tissue in control animals lacked the normal fibre orientation and cellularity. SEM of perichondral menisci showed surface characteristics similar to those of normal sheep menisci without fissures and lacerations; the control specimens had these defects. The femoral and tibial cartilage in contact with the new menisci had normal surface characteristics apart from one animal with slight surface irregularities. Control animals showed superficial lesions after three months which increased at six to 12 months postoperatively. Microangiography of the newly grown tissue demonstrated a less intense vascularisation after three months when compared with normal menisci. The failure stress and tensile modulus of perichondral menisci were significantly lower than those of normal contralateral menisci, and spontaneously regenerated tissue in meniscectomised animals had even lower values. There were no significant differences in values between newly grown perichondral menisci and spontaneously grown tissue.

Pressure distribution at the ankle joint.

Biomechanical factors such as trauma or overweight are discussed in relation to the aetiology of osteochondral lesions. As a consequence of the possible influence of these factors on joint loading patterns the pressure distribution on the load-bearing ankle joint has been investigated in a cadaveric biostatic model. By creating different joint positions with and without either lateral or medial ligament dissection, mimicking a ligamentous supination or pronation trauma, the pressure distribution under these various loading conditions was determined using pressure-sensitive film. The location of transduced contact area, the size and the amount of pressure was evaluated during the study. The results show that the location of the contact area was dependent on the joint position. Even without ligament dissection there was a minimum of contact area in the varus and the supination position with a pressure maximum lying on the medial border of the talus. Ligament dissection of the lateral ligaments resulted in an increased contact area in all the joint positions except for the varus and the supination position. In addition, the pressure increased significantly in the dorsal extension, varus and supination positions following lateral ligament dissection. Medial ligament dissection yielded results opposite to those observed with the lateral ligament dissection. The pressure maximum was observed to be, in the valgus and pronation position, on the lateral talar border with a significant increase of the pressure maxima following ligament dissection.

Renal hemodynamics and cardiovascular reactivity in the prehypertensive stage.

To examine whether sympathetic nervous activation has an impact on renal circulation in subjects at risk for high blood pressure, we assessed renal hemodynamics and cardiovascular response to mental stress in 40 healthy young white males, 12 normotensive subjects without and 14 with familial hypertension, and 14 with borderline hypertension. The response of systolic and diastolic blood pressure to mental stress was assessed while each patient performed a mental arithmetic task; this was taken as the parameter for the activation of the sympathetic nervous system. Renal plasma flow was measured by para-aminohippuric acid clearance under steady-state conditions. In parallel, glomerular filtration rate as a parameter for functional impairment of the kidneys was determined by creatinine clearance, and filtration fraction was also calculated. Patients with borderline hypertension were characterized by a reduced renal blood flow and increased filtration fraction in comparison with both normotensive groups. The increase in systolic blood pressure during mental stress was more pronounced in borderline hypertensives. We observed no significant difference in renal hemodynamics and cardiovascular response to mental stress between normotensives with and without a family history of hypertension. In the total population, cardiovascular response to mental stress was correlated with renal hemodynamics: The greater the increase in systolic blood pressure during mental stress, the lower was the renal plasma flow and the greater the filtration fraction. Thus, renal plasma flow was found to be already reduced and filtration fraction increased before sustained hypertension developed. Because this pattern in renal hemodynamics was related to cardiovascular response to mental stress, our data suggest that sympathetic activation already appeared to affect renal hemodynamics at the onset of essential hypertension.